S048171_MARYA_THESIS

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CRANFIELD UNIVERSITY
Laxmi Maurya
A Randomized Pilot Study to Compare
The Effectiveness of Etodolac and Combination of
Etodolac with Diazepam in Treating the Patients
Suffering
From Fibromyalgia
SCHOOL OF HEALTH
MSc THESIS

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CRANFIELD UNIVERSITY
SCHOOL OF HEALTH
MSc THESIS
Academic Year 2007-2009
Laxmi Maurya
Student id : s048171
The Effectiveness of Etodolac and Combination of
Suffering
From Fibromyalgia
Supervisor: Dr. Lincy Jaison
AUGUST 2009
This thesis is submitted in partial fulfillment (35%) of the requirements
For the degree of Master of Science
© Cranfield University 2005. All rights reserved. No part of this publication may be
reproduced without the written permission of the copyright owner

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ABSTRACT
Background: Fibromyalgia is a musculoskeletal pain disorder of unknown etiology which is
mainly characterized by chronic widespread pain and the presence of 11 to 18 tender points,
even the slight pressure on the tender points can cause terrible pain. Fibromyalgia syndrome
(FMS) has an estimated prevalence in North America and Europe of 0.5% to 5.8%. The
prevalence seems to increase up to 7% with increase in the age for both sexes.
Aim: To compare the effectiveness of etodolac and combination of etodolac and diazepam in
treating the patients suffering from Fibromyalgia
Methods: Around 90 Patients were enrolled and then screened 50 of them were excluded on
the basis of exclusion criteria and only those patients who met inclusion criteria were
randomized in 1:1 ratio to avoid any kind of bias. It was a pilot study 20 patients were
allocated in each group so which totals up to be 40 patients in both the groups.
Patient who took part in the study signed the informed consent which was explained with
study procedures to them by the PI of the study. All patients completed the study which
comprised of four visits, screening visit, end of treatment, follow up 1 and the last follow up
2 visit in the interval of 10 days (+1 day)
After signing the ICF data was collected from the patient on VAS score, FIQ, PSIQ & BPI
questionnaire administered to them
Results: Maximum patients participated were from the age group of 30 to 40 years (70%)
Through demographic data we found that women participation was more compared to men.
There is about 30-40 % difference in both the groups from visit 1 to visit 2 which is latter
on maintained on well in group B This shows there is mean decrease in Fibromyalgia
Imapct from visit 1 visit 2. Even BPI score have reduced from visit 1 to visit 2 but here the
scores are equal in both the groups. PSQI has shown remarkable difference in both the
groups Group B is quite ahead than Group A in few instances, group B has maintained the
improvement from visit 1 to follow-up 2 visit. Lowering the pain intensity
Conclusion:
This study proves that the combination of etodolac and diazepam is better than etodolac
alone. Group B has shown improvement in the sleep disturbance faced by the patients
suffering from Fibromyalgia hence further more studies should be conducted on this
combination treatment to make it successful.

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ACKNOWLEDGEMENT
I would like to take this opportunity to extend my thanks to all of those who helped and
guided me to complete my thesis.
First of all I would like to thank my mentor Dr lincy, for her help for finding a right topic for
my thesis. I am also thankful to her for her guidance and support through out this project.
A special thank to Dr. Pravina Koteshwar, Principal of ICRI and Mrs. Swapna G, course
Coordinator for being supportive and kind.
I would like to give my special gratitude to Dr. P.K.Raju, Assistant professor in Bangalore
Medical College, for permitting me to conduct my project at his clinic. As a industrial
supervisor, his co-operation and support was always there. I must thank him for giving his
valuable time for the correction of my project and for being very humble, without whom this
project would not be a success.
I must thank Dr. Narshimha Murthy for his help and guidance for the completion of my
project.
I would also like to thank Dr. KP Suresh for his support and valuable time.
I must also thank participants who gave their consent for using their data for my project.
I would like to express my thanks to Sufia for her support and help and for being with me
through out the project.
Finally I would like to express my special gratitude to my parents and family for supporting
and being with me always.

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TABLE OF CONTENTS
Abstract …………………………………………………………………………………. 3
Acknowledgement……………………………………………………………………….. 4
Table of contents…………………………………………………………………………5
List of abbreviations……………………………………………………………………...6
List of tables………………………………………………………………………………7
1 INTRODUCTION AND LITERATURE REVIEW
1.1 Introduction…………………………………………………………………………..8-10
1.2 Literature review……………………………………………………………………..10-19
2 AIM AND OBJECTIVES
Aim………………………………………………………………………………………..20
Objectives…………………………………………………………………………………20
3 MATERIALS AND METHODS
3.1 Study design/ methodology…………………………………………………………. 21
3.1.1 Material and document preparation………………………………………………21
3.2 Study population……………………………………………………………………..22
3.2.1 Inclusion criteria…………………………………………………………………..22
3.2.2 Exclusion criteria……………………………………………………….…………22
3.3 Ethic committee approval……………………………………………….……….…22-23
3.4 study conduct………………………………………………………….……………..23
3.5 Statistical methods……………………………………………………………………24
3.5.1 Sample size calculation……..………………………………………………………24.
3.5.2 Analysis…………………………………………………………………………….. 24
4 RESULTS………………………………………………………………………………25-41
5 Discussion and Limitation of the stud
5.1 Discussion…………………………………………………………………………....42-43
5.2 Limitations……………………………………………………………………………44
6 Conclusion and Future work
6.1 Conclusion…………………………………………………………………………….45
6.2 Future work…………………………………………………………………………...45
7 References…………………………………………………………………………….46-48
8 Appendices……………………………………………………………………………….49

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LIST OF ABBREVIATIONS
ACR = American College of Rheumatology
CFS = Chronic Fatigue Syndrome
CNS = Central Nervous System
COX e = Cyclo Oxygenase Enzyme
CRF = Case Report Form
IBS = Irritable Bowel Syndrome
FDA = Food and Drug Administration
FM = Fibromyalgia
FMS = Fibromyalgia Syndrome
HGH = Human Growth Hormone
HPA axis = Hypothalamic-Pituitary-Adrenal
ICF = Informed Consent Form
MDD = Major Depressive Disorder
MPS = Myofascial Pain Syndrome
NSAIDs = Non-Steroidal Anti- Inflammatory Drugs
PI = Principal Investigator
SSRIs = Selective Serotonin Reuptake Inhibitors
TMJ = Temporomandibular joint
VAS = Visual Analogue Scale

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LIST OF TABLES
Table 1: Comparison of age distribution ……………………………………………………………25
Table 2: Comparison of Gender distribution ………………………………………………………..26
Table 3: Marital status…………………………………………………………………………………26
Table 4: Religion………………………………………………………………………………………..26
Table 5: Education……………………………………………………………………………………..27
Table 6: Occupation……………………………………………………………………………………27
Table 7: Duration of disease…………………………………………………………………………..28
Table 8: Comparison of VAS score ………………………………………………………………….28
Table 9: PSQI …………………………………………………………………………………………..29
Table 10: PSQI …………………………………………………………………………………………29
Table 11a: PSQI ………………………………………………………………………………………..30
Table 11b: PSQI ………………………………………………………………………………………..30
Table 11c: PSQI…………………………………………………………………………………………31
Table 11d: PSQI…………………………………………………………………………………………31
Table 11e: PSQI…………………………………………………………………………………………32
Table 11f: PSQI…………………………………………………………………………………………32
Table 11g: PSQI…………………………………………………………………………………………33
Table 11h: PSQI…………………………………………………………………………………………33
Table 11i: PSQI………………………………………………………………………………………….34
Table 11j: PSQI………………………………………………………………………………………….34
Table 12.1 BPI…………………………………………………………………………………………...35
Table 12.2 BPI…………………………………………………………………………………………..35
Table 12.3 BPI…………………………………………………………………………………………..36
Table 12.4 BPI…………………………………………………………………………………………..36
Table 12.5 BPI………………………………………………………………………………………… 37
Table 12.6 BPI…………………………………………………………………………………………..37
Table 12.7 BPI…………………………………………………………………………………………..38
Table 12.8 BPI…………………………………………………………………………………………..38
Table 12.9 BPI…………………………………………………………………………………………..39
Table 12.10 BPI………………………………………………………………………………………….39
Table 13: FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)……………………………………40
Table 14: Brief Pain Inventory (Short Form)…………………………………………...41

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1. INTRODUCTION AND LITERATURE REVIEW
1.1 Introduction:
Fibromyalgia is a musculoskeletal pain disorder of unknown etiology which is mainly
characterized by chronic widespread pain and the presence of 11 to 18 tender points, even the
slight pressure on the tender points can cause terrible pain. Chronic widespread pain sleep
disturbances and headaches are among the few characteristic which differentiate FM from
rheumatoid arthritis and osteoarthritis. Fibromyalgia symptoms are not restricted only to the
pain it is often accompanied by many other non specific symptoms, such as irritable bowel
syndrome (IBS), chronic fatigue syndrome (CFS), sleep disturbances, and depressive mood
also known as Fibromyalgia Syndrome (FMS). (Wolfe. F. et al, 1990)
Fibromyalgia is the second most common medical conditions seen by rheumatologists. It is a
multifaceted disorder usually misunderstood as rheumatic condition due to unclear diagnosis.
There is no mono therapy present to treat FM even FDA has not approved any drug for
treating FM, till now the medication given is customized according the patients condition
nothing specifically given many studies showed combination therapy has been proved better
in relieving FM condition. Medication therapy alone has shown 30% to 50% improvement in
patients Treatment with alprazolam combined with ibuprofen demonstrated modest
improvement. (Russell I.J. et al, 1991)
The quality of life of patients is severely disturbed and functional and work disabilities are
serious concerns of patients suffering from FM (Henriksson. C. et al, 2000). This illness can
severely degrade the quality of life of patients and imposes high economic burden on the
society. In a multicenter outcome study, 538 patients were prospectively observed for 7
consecutive years. Patients with FM averaged 10 outpatient medical visits per year and used
a mean of 3 FM-related drugs. The mean yearly per patient cost in 1996 dollars was $2274,
similar to costs for the treatment of osteoarthritis. (Wolfe F. et al, 1997) According to the
prospective study of the American College of Rheumatology in 1990, they have defined the
classification for diagnosing fibrmyalgia other FM distinctive features are: fatigue, sleep
disorders, morning stiffness, paresthesias, anxiety, headache, irritable bowel, dryness in
eyes/mouth, and Raynaud phenomenon.2

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About Etodolac:
Generic Name: Etodolac & Brand Name: Lodine
Drug class and mechanism:
The FDA approved etodolac in January 1991. It comes under the class of NSAIDs this class
of drugs is used to treat mild to moderate pain and inflammation. The prostaglandins levels
are reduced which are chemicals responsible for the fever and tenderness occurs with
inflammation. The member drugs are Ibuprofen, Naproxen, Indomethacin, and nabuametone.
Etodolac acts on prostaglandins by blocking them resulting in lower level of cyclooxygenase
and lowers the pain and tenderness. Etodolac is available in 200 mg and 300 mg Capsules,
400 mg & 500 mg tablets and extended release in 400, 500 & 600 mg. Etodolac is mainly
prescribed for the treatment of inflammation and pain of osteoarthritis & rheumatoid arthritis
it is also used to cure tenderness of muscles and even menstrual cramps The dosing ranges
from the minimum 200 mg to the maximum dose of 1000 mg daily
Drug Interaction:
The most common drug interactions are jotted down here
Etodolac increases the level of lithium in blood as it blocks the elimination of lithium from
the body which leads to lithium toxicity. It is also seen that Etodolac reduces the blood
pressure because of prostaglandin reduce level. When etodolac is combined with gentamicin
it increases the level of aminoglycoside in blood, causing aminoglycoside related side
effects. Etodolac should be avoided by the patients who are taking blood thiners because
even etodolac thins the blood which can lead to excessive thinning of the blood and then into
bleeding
Side effects: the side effects related to etodolac are rash, headaches, dizziness, abdominal
pain, diarrhea & drowsiness. Etodolac thins the blood hence while any injury there are
chances that excessive bleeding may happen. It may also cause stomach ulceration and even
intestinal bleeding. Etodolac reduces the blood flow to kidneys causing kidney impairment.
About Diazepam: Diazepam first marketed as Valium by Hoffmann- La Roche is a
benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative,

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skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety,
insomnia, seizures, muscle spasms, alcohol withdrawal.
Dosage available ranges from 2mg to 10 mg once or twice daily can be given to the patients
according to the condition. Available in market in tablet injection form as well. Special
caution should be taken when administered in small children It has been shown in a clinical
study that between 50–100% of patients on low-dose long-term diazepam therapy are
physically dependent on their medication, and experience withdrawal symptoms upon
discontinuation from a dose taper (Rickels K et al, 1990)
1.2 REVIEW OF LITERATURE:
We reviewed the literature of the past years to know the recent developments in prevalence,
diagnosis, pathogenesis, and treatment. Special attention given to the studies related to the
sleep disturbances in FM. searching out the best available treatment in past and in present.
Fibromyalgia:
Fibromyalgia (FM)) is known as a complex, chronic condition which causes mainly
widespread pain and many other symptoms. Lets know what does it mean Fibromyalgia
=“fibro” fibrous tissues (soft tissues), +“myo” (muscles), + “algia” (pain). FM is always
confused with Arthritis hence the major difference in them is that FM does not cause any
swelling or pain in the joints. FM symptoms are not visible it is only characterized by the soft
tissue pain around the joints, skin and around the body organs. The pain due to FM is
generally accompanied with muscle spasm hence also known as musculoskeletal pain
disorder. The location and intensity of pain may change daily it becomes severe in parts of
the body which are used more like neck, legs and shoulders. The pain intensity can be so
severe that it can interfere in performing the simplest tasks in day to day life otherwise causes
moderate discomfort. The same way the fatigue is also felt mild - moderate - severe (flu like
tiredness) Till now no physical deformity is know due to FM.
What causes Fibromyalgia:
The exact causes of fibromyalgia in not known till now but there are several hypothesis
developed which might be causing FM.
Genetic predisposition: Some studies have showed evidence that genetic factors play role in
developing fibromyalgia. There is high aggregation of FM is seen in families most probably
said polygenic (Stormorken H. et al, 1992)

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Stress : stress increases the chances to develop fibromyalgia, where it alters the function of
HPA axis (hypothalamic-pituitary-adrenal)
Central dopamine dysfunction (hypodopaminergia): The central abnormality is responsible
for symptoms of FM according to Dopamine hypothesis. It’s a catecholamine
neurotransmitter which plays main role in pain perception like natural analgesia
Abnormal serotonin metabolism: Researchers hypothesized, in 1975 that serotonin, a
neurotransmitter which regulates sleep patterns, mood, concentration and pain, could be
involved in the pathophysiology of fibromyalgia-associated symptoms. (Michalek JE. et al,
1992)
Deficient human growth hormone (HGH) secretion: caused by the deficiency Human
growth hormone
Psychological factors: Major depression is directly associated with FM there are similarities
in neuroendocrine abnormalities, physiological symptoms and fibromyalgia. Education,
attitude change, and in some cases, psychotherapy are proposed as treatments. (Sarno. D.r.
et al, 2006)
Prevalence:
Fibromyalgia syndrome (FMS) has an estimated prevalence in North America and Europe of
0.5% to 5.8%. [4] Health conditions of unknown etiology that predominantly affect middle-
aged adults, women are affected more than men the ratio is 9:1. The prevalence seems to
increase up to 7% with increase in the age for both sexes. (Bergman S, et al, 2001)
An Internet based survey done for fibromyalgia epidemiology study on approx 2,600 people
reported that the most frequently observed factors which have worsen the condition of the
patients suffering from fibromyalgia symptoms were emotional distress (83%), weather
changes (80%), sleeping problems (79%), strenuous activity (70%), mental stress (68%),
worrying (60%), car travel (57%), family conflicts (52%), physical injuries (50%) and
physical inactivity (50%) in decreasing order of percentage. Other factors included
infections, allergies, lack of emotional support, perfectionism, side effects of medications,
and chemical exposures. (Bennett RM, et al, 2007)
Diagnosis:

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Fibromyalgia is known as soft tissue rheumatism, generalized pain in the joints, muscles and
spines. It is said that pain originates from ligaments and soft tissues patients it is difficult to
diagnose FM but, who are suffering experiences morning stiffness, on physical investigation
no signs of inflammation even the erythrocyte sedimentation rate is normal. In old time FM
was diagnosed with inflammation which was not correct FM being a non-articular with non-
inflammatory condition, fibromyalgia is atypical entity in the field of rheumatology, only a
medical specialty dealing typically with articular, inflammatory diseases can deal with it who
will be able to discriminate between the FM condition and other rheumatic conditions or
other diseases. Only they can investigate if any underlying primary conditions are there such
as hyperthyroidism. There are no such specific diagnostic criteria for fibromyalgia. Diagnosis
is done on the basis of below mentioned symptoms and tender points, and excluding any
other condition causing the same symptoms. Fatigue (90%), morning stiffness (80%), sleep
disturbances (80%), paraesthesias (60%), headache (50%), anxiety (50%), and irritable bowel
(40%) (Rasker JJ et al, 1996) However, classification criteria are there, which says the
presence of widespread pain and tender points is must (Wolfe. F. et al, 1990). Patient
suffering from FM will respond badly if even slightly pressed at the tender areas while
physical examination. 1990 American college of Rheumatology (ACR) developed a
classification to diagnose FM describing 18 tender/trigger pints to harder you press the better
you find FM.
Treatment Available:
The fibromyalgia treatment varies from patient to patient, only symptomatic treatment is
available there is no medication present which can prevent or treat fibromyalgia. The
treatment is generally tailor made where medical practitioners treats the patient accordingly.
The most common treatment strategies used alone or in combination, are:
Prescription Medications
Analgesics & Narcotic medications (opioids):
Analgesics are drugs that are most commonly used to relieve pain. acetaminophen (Tyenol)
anti-inflammatory medications with analgesic properties, Recently Tramadol seems to
becoming popular in market due to its effectiveness in relieving pain by directly acting on
brain where pain signals are received or stronger narcotic drugs containing codeine is also
effective but they are prescribed less by the doctors due their addictive qualities. Narcotic
drugs are sometimes combined with acetaminophen for added strength to combat the painful

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flare ups. Patients using this medication should be aware that codeine may cause allergic
reactions and even seizures.
used in fibromyalgia treatment are:
1. Vicodin (hydrocodone + acetaminophen)
2. Darvocet (propoxyphene napsylate)
3. Oxycontin (oxycodone hydrochloride)
4. Percocet (oxycodone + acetaminophen)
Even opioids seems to be helpful in treating acute FM but not in chronic conditions as they
do not eradicate pain from root hence the problems related to FM in not taken care and the
patients condition gets worsen, Long term narcotic analgesics are preferred over short term
acting drugs as theirs effect lasts only for a night and then wears off.
Anti-inflammatory medications
The most traditional one is NSAIDs (Non-Steroidal Anti- Inflammatory Drugs) as we know
in FM inflammation is not seen only the analgesic property of this class of drugs is useful to
the patients available with prescription or without it as well. Long term use of NSAIDs can
cause bleeding, gastrointestinal ulcers. These drugs causes stomach irritation hence doctors
prescribe NSAIDs to be taken with food.
Patients can now rely more on this class of drugs due to the COX-2(bad) inhibitor coming in
picture, which blocks only one of the COX enzymes maintaining the high levels of
prostaglandins. Rise in its level can cause inflammation and pain whereas the COX 1 (good)
mainatains the body organ and other tissues in good shape. No side effects are seen against
COX-2 Inhibitors. Celebrex manufactured by Searle Pharmaceuticals and Vioxx by Merck
only sold by prescription.
Among the traditional prescription with their generic names NSAIDs are:
1. Indocin (indomethacin)
2. Naprosyn (naproxen)
3. Voltaren (diclofenac)
4. Daypro (oxaprozin)
5. Toradol (ketorolac)
6. Feldene (piroxicam)
7. Relafen (nabumetone)
8. Lodine (etodolac)

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9. Orudis (ketoprofen)
10. Mobic (meloxicam)
Tricyclic anti-depressants
Tricyclic anti depressants enhance the brain neurochemical serotonin levels which lacks in
patients suffering from FM. They attained the popularity due to controlling pain and inducing
sleep which was the major concern of FM. The dose prescribed is lower in patients suffering
from FM than doses given to patient suffering from depression.
Commonly used Tricyclic’s are:
1. Desyrel (Trazadone)
2. Elavil (Amitriptyline)
3. Pamelor (Nortriptyline)
4. Sinequan (Doxepin)
The known side effects are: dry mouth, drowsiness, morning hangover, constipation, weight
gain, and sometimes anxiety. Because of their sedating qualities, tricyclics are usually taken
at bedtime.
Selective Serotonin Reuptake Inhibitors (SSRIs)
This class of drugs not only boosts the serotonin levels but even maintains those level in the
system for longer time once it is released from the brain. Theses drugs mainly deals with
Fatigue, depression, and cognitive impairment caused due to FM generally taken durin
morning times It causes nervousness, insomnia, dry mouth, headache, nausea, diarrhea, and
in the case of Zoloft and Paxil, sexual dysfunction.
Some known SSRIs include:
1. Prozac (fluoxetine)
2. Serzone (nefazodone hydrochloride)
3. Zoloft (sertraline)
4. Celexa (citalopram hydrobromide)
5. Paxil (paroxetine)
A study published in Arthritis & Rheumatism, In 1996 a research team headed by Don
Goldenberg, M.D., found that not only were the tricyclic Elavil and the SSRI Prozac each
effective in the treatment of fibromyalgia, but when used as a combination treatment, they

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worked better than either medication alone. Since then, prescribing a SSRI drug during the
day and a tricyclic at night has become a new tool in the management of fibromyalgia.
Muscle relaxants
FM is a musculoskeletal disease and muscle relaxants are proved to be very effective they
minimize the muscle spasm and pain in the muscles another plus point is they induce sleep
due to their sedating qualities. Mostly given at night time. The known side effect includes
drowsiness, dry mouth, constipation, headache, and heart palpitations.
Typically used muscle relaxants are:
1. Flexeril (cyclobenzaprine hydrochloride)
2. Norflex (orphenadrine citrate)
3. Soma (carisoprodol)
4. Skelaxin (metaxalone)
5. Robaxin (methocarbamol.
Anti-convulsant medications,
Mainly used to treat epilepsy sometimes even used to relief neuropathic pain the burning or
electric shock like feeling in FM. Gives relief from nerve irritation
1. Neurontin (gabapentin)
2. Depakote (divalproex)
3. Dilantin (phenytoin)
4. Tegretol (carbamazepine)
Most common side effects include sedation, dry mouth, and dizziness. Patients should be
under supervision to monitor blood counts and liver function. GABA. Lyrica has been shown
to improve pain, disturbed sleep, and fatigue in a recent FM study (Arthritis & Rheumatism,
April 2005).
Sleep medicines
Generally used to treat insomnia and sleep related disorders. Many studies have proved the
sleep disorder is most commonly seen in FM patients. They find difficulty I falling asleep
hence sleep medicines are proved to be very effective the basic thing is to induce sleep
improve sleep and enhance day time functioning the drugs which are prescribed are the
central nervous system depressants Ambien (zolpidem tartrate) and Sonata (zaleplon).
Prescribed for short duration of time as it causes dependence. Recently found although not
yet approved by the FDA specifically for the treatment of fibromyalgia, the central nervous

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system depressant known as Xyrem is a promising drug currently being assessed for use in
individuals with FM.
Benzodiazepines,
Usually given at the bed times as it is very sedating makes the patient feel calmer and
relieves from pain due to muscle relaxants properties Like the narcotic analgesics,
benzodiazepines can cause physical dependency and must be administered under supervision.
1. Klonopin (clonazepam)
2. Valium (diazepam)
3. Restoril (temazapam)
4. Xanax (alprazolam).
Physical Rehabilitation:
There are many know physical therapies given by the trained physical rehabilitation
professionals, who know the FMS best some people even practice it at home like traditional
Kerla Auyrvedic massage in India particularly under the supervision of a professional.
Among the most widely used therapies are the following:
Massage:
Includes the application of hot and cold packs to increase the blood circulation, sore muscles,
it removes the built up toxins like lactic acid in the muscles and rejuvenate them which have
undergone mechanical damage its is often accompanied with ultrasound for better results.
Trigger Point Therapy:
This therapy breaks the trigger points in the muscles where the nervous system is
hyperactive. The therapist applies the sustained pressure over the affected area. There are
trigger point injections also given when this therapy doesn’t work on the patients.
Craniosacral Therapy:
It is a gentle non invasive therapy to enhance the Craniosacral system, this therapy enhance
the body’s natural healing mechanism
Developed by Dr. John Upledger, craniosacral therapy is "a gentle, non-invasive method of
evaluating and enhancing the function of the craniosacral system, the environment in which
the brain and spinal improves CNS despite the negative energy due to stress.
Flexyx Neurotherapy:
A newly discovered therapy to treat FM by Dr. Stuart Donaldson, Flexyx Neurotherapy
essentially "resets" the brains of FMS patients who show signs of "EEG Slowing" (see
Section 5 of this document) using a non-light emitting diode which is transmitted to the

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brain, drawing power from the slowest brain waves up to the fastest waves. Once the brain
enters a flexible new state, effective neuromuscular re-education, including trigger point
therapy, myofascial release, and micro exercises can be instituted.
Chiropractic:
It controls all bodily functions specially brain, spinal cord, and nerves, this therapy removes
the blockages in the nerves and allow the body to heal in a healthy and natural way
Osteopathy:
A system of therapy founded by Andrew Taylor Still, osteopathy states that the body is often
able to effectively overcome with disease on its own as long as it is functioning normally and
is in a has a favorable environment, and there is no nutritional deficiency. It mainly emphasis
on musculoskeletal system
Stretching:
The physical therapist or patient themselves performs gentle stretching there are many
videotapes launched so that FM patient can perform it while at home. Stretching improves
muscle tension and spasms. On most affected areas Spray and stretch method can be used
where you first apply the pain reliever and then stretch gently.
.Aerobic Exercise:
An exercise with low impact is a boom for FM patients it promotes blood circulation and
provides oxygen and other nutrients the muscles and connective tissues. There are many
health centres where low impact aerobic is taught like walking, warm water walking,
treadmills, more of gentle exercise. To start FM patients should do mild exercises and then
slowly built up the stamina. Medical practioner have suggested that the exercises should be
done regularly for better results however exercising may enhance the pain of the patient
hence a physical rehabilitation therapist supervision is required
Complementary Therapies: A number of other approaches have also been proven effective
and useful in the management of Fibromyalgia syndrome
Occupational Therapy:
Due to the long hours Jobs relating to task which contributes or enhance pain for which an
occupational therapist can help by suggesting/designing improvements. Increasingly,
literature is also available on this subject. For example, for Fibromyalgia patients who work
at a computer, ergonomic keyboards, chairs, and other products may provide significant
relief

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Relaxation Therapy:
This therapy is not directly treating FM but it has an indirect way by relieving the significant
stress generated due to FM , studies have proved it that a FM patient can not manage his/her
stress level and worsen their condition because of stress Thus, effective stress management
programs are important. Among those used for Fibromyalgia are: biofeedback, watsu,
meditation, breathing exercises, progressive relaxation, guided imagery, and autogenic
training. Initially patient need training and latter on can continue once they have learned it
well. There are books, audio and video tapes available to teach relaxation techniques. The
most common techniques is Meditation.
Nutrition:
You must be wondering how Nutrition will help in treating FM, Nutrional therapy focuses on
getting rid of body toxins through diet or by restoring body nutrients which are lacking in
body. The diet must include Antioxidant Vitamin supplements to fight against stress and
enhance the immune system
The consumption of sugar, coffee, and alcohol is restricted to a limit and more nutritional
diet like toxin cleansing are given more but again this can be done under the guidance of a
dietician, who is familiar with FMS
needs of a patient. As with other Fibromyalgia treatments, a specifically designed nutritional
plan that works well for one patient may prove disastrous for another.
Acupuncture:
A treatment which involves the insertion of very small needles at specific anatomical points
identified as conducive to energy, has received more scrutiny. In November 1997, the
National Institutes of Health convened a Consensus Panel on Acupuncture which issued a
statement indicating that pain from musculoskeletal conditions and nausea were the entities
most successfully treatable with acupuncture.30 In February 1998, the NIH Office of
Alternative Medicine, along with NIAMS and several other institutes/offices announced the
"Acupuncture Clinical Trial Pilot Grants" designed to increase the quality of clinical research
evaluating the efficacy of acupuncture for the treatment or prevention of Fibromyalgia and
several other diseases/conditions.
Cognitive/Behavioral Therapy:
It depends on the patient attitude whether he will be able to manage FM, attitude is often one
of the strongest predictors. Patients who are not actively engaged in taking charge of their
illness simply aren't as likely to get better. Who wants help seeks through exercise, physical

19
therapy, or medications. Those who need help in fighting to over come negative thinking can
find help via classes and/or audio tapes on cognitive/behavioral therapy or via counseling.
There is a proverb “GOD helps those, who help themselves”.
New Drugs under Investigation
Till date there is no medication been approved by the FDA specifically for treating the FM
condition, so only symptomatic treatment is given and drugs of other illness are used by
knowing the symptoms but now many companies/ pharmaceutical companies are working on
developing a drug for fibromyalia. Currently the investigation is going on:
Milnacipran: A selective serotonin and norepinephrine reuptake inhibitor being tested in
clinical trials by Cypress Bioscience for possible FDA approval.
Pramipexole & Ropinorole: Dopamine agonists being studied by Andrew Holman, M.D., at
the University of Washington (Seattle).
The main purpose of this study is to compare and find out which treatment is more effective
in treating fibromyalgia better, etodolac alone or combination of etodolac and diazepam.

20
2. AIM AND OBJECTIVES
Aim: To compare the effectiveness of Etodolac or a combination of Etodolac + diazepam in
treating patients suffering from Fibromyalgia
Primary objective:
The main objective of this is to find out the best treatment for fibromyalgia among etodolac
and combination of etodolac and diazpem
Secondary Objectives:
1. To find out the effectiveness of Etodolac in treating FM
2. To find out Improvement in sleep disturbances in fibromyalgia patients by taking
diazepam.
3. To find out how many patients require continuation of medication after the 10th
day of
the treatment.

21
3. MATERIAL AND METHODS
Research and Methodology:
3.1 Study design/ Methodology:
This study was conducted in a single centre at Sushruta Orthopaedic Centre in Bangalore.
This site was selected to conduct this study because populations required for this study were
easily available in this clinic as it’s a specialized clinic for this kind of condition. Every day
many patients visit this clinic. Because of the good patient pool enrolling patient in this study
was easy.
Study was prospective- interventional pilot study, where we made two groups which
underwent the treatment. One group was assigned with group A (etodolac 400 mg tab) alone
and other group B with combination of etodoalc(400 mg tab) and diazepam(5mg)
Around 90 Patients were enrolled and then screened 50 of them were excluded on the basis
of exclusion criteria and only those patients who met inclusion criteria were randomized in
1:1 ratio to avoid any kind of bias. It was a pilot study 20 patients were allocated in each
group so which totals up to be 40 patients in both the groups.
Patient who took part in the study signed the informed consent which was explained with
study procedures to them by the PI of the study. Thankfully all the patients completed the
study which comprised of four visits, screening visit, end of treatment, follow up 1 and the
last follow up 2 visit in the interval of 10 days (+1 day)
After signing the ICF data was collected from the patient on questionnaire given to them
.
3.1.1 Material and Document preparation:
Preparation of case report form (CRF):
With the help of Dr. Narshimha Murthy, we prepared the CRF which could gather the
patients demographic details. This data was very much required like Age, gender, religion,
work, education
Preparation of Informed consent document:
Informed consent form was prepared to obtain the written informed consent from the patients
and it was developed by the help of my mentor.

22
3.2 Study population:
In this study patients with suffering from Fibromyaglia disease were included. Who met the
inclusion Criteria, since it was a pilot study 20 patient in each group were recruited both male
and female aged 18 to 65 years were included.
Inclusion criteriaand exclusion criteria:
Vigorous search of literature was done to narrow down the inclusion & exclusion criteria
keeping in mind the condition of FM and the treatment groups my mentor and PI helped me
in this as well. After the amount of work we did on it we found few inclusions and exclusion
criteria which are listed down:
3.2.1 Inclusion Criteria:
1. Patients Diagnosed of Fibromyalgia according to the American College of
Rheumatology Criteria.
2. Newly Diagnosed Fibromyalgia Patients < 3 months time.
3. Pain intensity marked on VAS greater or equal to 4 (on 0 -10 scale)
4. Both gender
5. Age 18 to 65
6. Literate person, who can understand and comply with the requirements of the study.
3.2.1 Exclusion criteria:
1. Patient unwilling to give informed consent.
2. If pain is not primarily due to Fibromyalgia.
3. Pregnant or nursing mother.
4. Patient with any other chronic conditions.
5. Participation in other therapeutic trials.
6. Had diazepam or etodolac one week before the study
7. Patient working in night shift (11PM - 7AM).
8. Patient diagnosed with sleep disorder earlier.
9. Patient undergoing any complementary therapy.
3.3 Ethics committee approval:
Prior to commencement of the study scientific approval from ICRI committee was taken then
permission from the Dr.P.K.Raju to conduct the study at his clinic and then latter on
submission was done to the ethics committee of Bangalore Medical College. Ten copies
protocol, CRF, informed consent form, Fibromyalgia Impact questionnaire, sleep Index

23
questionnaire, Brief inventory Pain questionnaire were submitted to the ethics committee for
their review. It took around a month’s time for them to review and then approve the study.
3.4 study conduct:
This study was designed to assess and compare the effectiveness of treatment Etodolac alone
with combination treatment of Etodolac and Diazepam hence, it is randomized to avoid any
kind of bias. After screening & enrollment, randomization will be done. Group A given
orally 400 mg Tab Etodolac for 10 days consecutively every night before going to bed.
Group B given Tab Diazepam orally 5 mg and Tab Etodolac (400mg) every night before
going to bed for 10 days.
Questionnaires will be administered to the patients after randomization, which will be at
baseline then, at the end of treatment (Day 10), & at Follow up visits (Day 20 & 30)
To find out efficacy patient will be administered questionnaires:
 Visual analogue scale from 0 to 10, where 0= no pain and 10= worst pain.
 Fibromyalgia Impact Questionnaire (FIQ)
 Pittsburgh Sleep quality Index (PSQI).
 The Brief pain Inventory.
After ethics committee approval data collection were started. Patient’s data were collected in
Case Report form and in questionnaires. Data were collected from patients file and direct
Treatment Time Frame For : Group A or
Group B
Day 0
Screening, Enrollment and randomization
Questionnaires Administered
Week 1
Start of Treatment Visit 1 either group A or Group B: Day 1 Questionnaires
Administered
Week 2
End of Treatment Visit 2: Day 10
Week 3
Follow-up Visit1: Day 20
Week 4
Follow-up Visit 2: Day28 +/- 2 days.

24
interaction with the patients. Demographics data and significant medical history of the
patients were collected. Before taking patient’s data written informed consent was taken from
the patients and their representative in case patients were not able to give their consent.
Information was given in the language that was understandable by the patients. Duration for
data collection in clinic was 1 month from 8th
Oct 2009 to 17th
of Nov 2009
3.5 Statistical method:
Sample size calculation:
Sample size calculated for this study was 90 in both the groups but due to lack of data and
time we made it a pilot study and calculated it to be 20 in each group.
3.5.1 Analysis:
Descriptive statistical analysis has been carried out in the present study. Results on
continuous measurements are presented on Mean  SD (Min-Max) and results on categorical
measurements are presented in Number (%). Significance is assessed at 5 % level of
significance. ,Student t test ( two tailed, independent) has been used to find the significance
of study parameters on continuous scale between two groups Inter group analysis) and
1. Student t test (Two tailed, independent)
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2.Significant figures
+ Suggestive significance (P value: 0.05<P<0.10)
* Moderately significant ( P value:0.01<P  0.05)
** Strongly significant (P value : P0.01)
3.5.2 Statistical software:
The Statistical software namely SPSS 15.0, Stata 8.0, MedCalc 9.0.1 and Systat 11.0 were
used for the analysis of the data and Microsoft word and Excel have been used to generate
graphs, tables etc.

25
4.RESULTS
The result chapter deals with the final outcomes of this study, which aimed to compare and
find out the effective treatment among the two groups of the study around 90 patients were
enrolled in the study but out that 50 were excluded as the didn’t met base line inclusion
criteria. Hence only 40 patients were recruited that is 20 patients in each group.
4.1 patient’s characteristics:
Table 1: Comparison of age distribution demonstrates that the participants were more from
the age group of 20 years to 40 years
Table 1: Comparison of age distribution
Age in years
Group A Group B Total
No % No % No %
21-30 7 35.0 4 20.0 11 55.0
31-40 6 30.0 8 40.0 14 70.0
41-50 3 15.0 3 15.0 6 30.0
51-60 4 20.0 3 15.0 7 35.0
>60 0 0.0 2 10.0 2 10.0
Total 20 100.0 20 100.0 40 200.0
Mean ± SD 38.50±11.10 41.30±13.04 39.90±12.04
Samples are age matched with P=0.488

26
Table 2: Comparison of Gender distribution
The Gender distribution states that in both the groups female participated more in this
study.
Gender
Group A Group B Total
No % No % No %
Male 8 40.0 10 50.0 18 45.0
Female 12 60.0 10 50.0 22 55.0
Total 20 100.0 20 100.0 40 100.0
Samples are gender matched with P=0.525
Table 3: Marital status
The marital status data states that married participants were more in both the groups as
compared to singe and widowers
Marital status
Group A
(n=20)
Group B
(n=20)
Total
(n=40)
No % No % No %
Single 5 25.0 2 10.0 7 17.5
Married 10 50.0 13 65.0 23 57.5
Widow 2 10.0 4 20.0 6 15.0
Divorced 3 15.0 1 5.0 4 10.0

27
Table 4: Religion
In both the groups Hindu Participants were more compared to Muslim & Christian
Religion
Group A
(n=20)
Group B
(n=20)
Total
(n=40)
No % No % No %
Hindu 8 40.0 12 60.0 20 50.0
Muslim 7 35.0 8 40.0 15 37.5
Christian 5 25.0 0 0.0 5 12.5
Table 5: Education
Participants were more from literate and degree group
Education
Group A
(n=20)
Group B
(n=20)
Total
(n=40)
No % No % No %
Literate 8 40.0 9 45.0 17 42.5
Degree 4 20.0 8 40.0 12 30.0
Post graduate 8 40.0 3 15.0 11 27.5
Table 6: Occupation
This table demonstrates that housewives and executives took part more when compared
to business, teacher and others
Occupation
Group A
(n=20)
Group B
(n=20)
Total
(n=40)
No % No % No %
Housewife 7 35.0 5 20.0 12 30.0
Business 3 15.0 4 20.0 7 17.5
Executive 8 40.0 4 20.0 12 30.0
Teacher 0 0.0 3 15.0 3 7.5
Others 2 10.0 4 20.0 6 15.0

28
Table 7: Duration of disease
As the study was on freshly diagnosed FM patients, very few suffered from the disease
more then 10 weeks
Duration in
weeks
Group A
(n=20)
Group B
(n=20)
Total
(n=40)
No % No % No %
1-5 weeks 15 75.0 9 45.0 24 60.0
6-10 weeks 5 25.0 9 45.0 14 35.0
>10 weeks 0 0.0 2 10.0 2 5.0
Table 8: Comparison of VAS score
There is significant difference from visit 1 to visit 2 maintained till follow up visit in bot
the groups. The pain intensity is decreased after the treatment. In group A the pain seems
to be relapsing as there is increase in the pain intensity after follow up visit 1 but in group
B it is maintained
VAS score Group A Group B P value
Day 1 7.60±1.09 7.70±0.80 0.744
visit 2 2.30±1.08 2.25±1.16 0.889
Follow up Visit 1 1.75±0.91 2.00±1.21 0.465
Follow up Visit 2 2.05±1.23 2.00±1.34 0.903

29
SLEEP QUALITY INDEX
Table 9: During the past month, what time have you usually gone to bed at night?
There is no significance change in the bed going time. Both the groups seems to be similar
Response
Group A Group B
Visit 1 Visit 2 Visit 3 Visit 4 % change Visit 1 Visit 2 Visit 3 Visit 4 % change
9-10PM 7 (35.0%) 3(15.0%) 6(30.0%) 3(15.0%) -20.0 7(35.0%) 7(35.0%) 6(30.0%) 6(30.0%) -40
10-11PM 9(45.0%) 13(65.0%) 10(50.0%) 13(65.0%) +20.0 6(30.0%) 6(30.0%) 7(35.0%) 7(35.0%) +40
11-12PM 4(20.0%) 4(20.0%) 4(20.0%) 4(20.0%) 0 7(35.0%) 7(35.0%) 7(35.0%) 7(35.0%) 0
Total 20(100.0%) 20(100.0%) 20(100.0%) 20(100.0%) 0 20(100.0%) 20(100.0%) 20(100.0%) 20(100.0%) 0
Table 10: During the past month, how long (in minutes) has it usually taken you to fall asleep each night?
Here we can see lot of change in group B in the second visit it self all patients were able to sleep within 10-20 mins even group shows
the result but group B is leading
Response
Group A Group B
Visit 1 Visit 2 Visit 3 Visit 4 % change Visit 1 Visit 2 Visit 3 Visit 4 % change
10-20mins 2(10.0%) 17(85.0%) 16(80.0%) 13(65.0%) +55.0% 2(10.0%) 20(100.0%) 19(95.0%) 18(90.0%) 80.0%
21-30mins 9(45.0%) 3(15.0%) 4(20.0%) 7(35.0%) -10.0% 12(60.0%) 0 1(5.0%) 2(10.0%) -50.0%
31-40mins 9(45.0%) 0 0 0 -45.0% 6(30.0%) 0 0 0 -30.0%
Total 20(100.0%) 20(100.0%) 20(100.0%) 20(100.0%) 0 20(100.0%) 20(100.0%) 20(100.0) 20(100.0%) 0

30
Table 11a: During the past month, how often have you had trouble sleeping because you . . . a) Cannot get to sleep within 30 minutes
In visit 1 maximum were not able to sleep within 30 mins but by the time treatment end patients were able to sleep well again Group B
is ahead.
Response
Group A Group B
Visit 1 Visit 2 Visit 3 Visit 4
%
change
Visit 1 Visit 2 Visit 3 Visit 4 % change
Not during past month 0(0%) 11(55%) 4(20%) 3(15%) 15 0(0%) 13(65%) 8(40%) 1(5%) 5.0
Less than once a week 0(0%) 9(45%) 12(60%) 7(35%) 35 0(0%) 7(35%) 10(50%) 14(70%) 70.0
Once or twice a weeks 6(30%) 0(0%) 4(20%) 10(50%) 20 9(45%) 0(0%) 2(10%) 5(25%) -20.0
Three or more times a week 14(70%) 0(0%) 0(0%) 0(0%) -70 11(55%) 0(0%) 0(0%) 0(0%) -55.0
Total 20 20 20 20 0 20 20 20 20 0
Table 11b: During the past month, how often have you had trouble sleeping because you . . b) Wake up in the middle of the night or
early morning
In Visit 1 Maximum patients were getting up in the middle of the night due to pain,after treatment this condition was improved
Response
Group A Group B
%
change
%
change
Not during past month 0(0%) 17(85%) 9(45%) 4(20%) 20 0(0%) 18(90%) 13(65%) 5(25%) 25
Less than once a week 1(5%) 3(15%) 11(55%) 13(65%) 60 2(10%) 2(10%) 7(35%) 13(65%) 55
Once or twice a weeks 10(50%) 0(0%) 0(0%) 3(15%) -35 7(35%) 0(0%) 0(0%) 2(10%) -25
Three or more times a week 9(45%) 0(0%) 0(0%) 0(0%) -45 11(55%) 0(0%) 0(0%) 0(0%) -55
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

31
Table 11c: During the past month, how often have you had trouble sleeping because you . . c) Have to get up to use the bathroom
The frequency of getting up in night time is more in Group A whereas Group B patients have not got up to use the bathroom since
they started medication
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 11d: During the past month, how often have you had trouble sleeping because you . d) Cannot breathe comfortably
In this parameter Group A seems to be better then Group B
Response
Group A Group B
%
change
%
change
Once or twice a weeks 7(35%) 0(0%) 2(10%) 3(15%) -20 4(20%) 0(0%) 3(15%) 8(40%) 20
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

32
Table 11e: During the past month, how often have you had trouble sleeping because you . . e) cough or snore loudly
The data for this table states that there is no significance difference between both the groups
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 11f: During the past month, how often have you had trouble sleeping because you . f) Feel too cold
Group A participants complained more about feeling cold as compare to Group B the instance was less than once a week
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

33
Table 11g: During the past month, how often have you had trouble sleeping because you . g) Feel too hot
Response
Group A Group B
%
change
%
change
Once or twice a weeks 3(15%) 0(0%) 7(35%) 8(40%) 25 8(40%) 0(0%) 3(15%) 5(25%) -15
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 11h: During the past month, how often have you had trouble sleeping because you h) Had bad dreams
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

34
Table 11i: During the past month, how often have you had trouble sleeping because you . i) Have pain
The data obtained has no remarkable difference in both the groups in visit 1 follwing the visits further more both the groups are
effective
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 11j: During the past month, how often have you had trouble sleeping because you j) Other reason(s), please describe__PAIN
WHILE SLEEPING____
Response
Group A Group B
%
change
%
change
Once or twice a weeks 5(25%) 0(0%) 5(25%) 6(30%) 5 5(25%) 0(0%) 2(10%) 5(25%) 0
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

35
Table 12: (6) During the past month, how would you rate your sleep quality overall?
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 12: (7) During the past month, how often have you taken medicine to help you sleep(prescribed over the counter)?
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

36
Table 12: (8) During the past month, how often have you had trouble staying awake while driving, eating meals, or engaging in social
activity?
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 12: (9) During the past month, how much of a problem has it been for you to keep up enough enthusiasm to get things done?
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

37
Table 12: (10) Do you have a bed partner or room mate?
Response
Group A Group B
%
change
%
change
Not during past month - - - - - - - - - -
Less than once a week - - - - - - - - - -
Once or twice a weeks 9(45%) 9(45%) 9(45%) 9(45%) 0 7(35%) 7(35%) 7(35%) 7(35%) 0
Three or more times a week 11(55%) 11(55%) 11(55%) 11(55%) 0 13(65%) 13(65%) 13(65%) 13(65%) 0
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 12: (11) If you have a room mate or bed partner, ask him/her how often in the past month you have had a) Loud snoring
Response
Group A Group B
%
change
%
change
Once or twice a weeks 11(55%) 0(0%) 2(10%) 2(10%) -45 6(30%) 0(0%) 4(20%) 7(35%) 5
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

38
Table 12: (11) If you have a room mate or bed partner, ask him/her how often in the past month you have had b) Long pauses between
breaths while asleep
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 12: (11) If you have a room mate or bed partner, ask him/her how often in the past month you have had c) Legs twitching or
jerking while you sleep
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

39
Table 12: (11) If you have a room mate or bed partner, ask him/her how often in the past month you have had d) Episodes of
disorientation or confusion during sleep
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0
Table 12: (11) If you have a room mate or bed partner, ask him/her how often in the past month you have had e) Other restlessness
while you sleep; please describe: Pain in joints_
Response
Group A Group B
%
change
%
change
Total 20(100%) 20(100%) 20(100%) 20(100%) 0 20(100%) 20(100%) 20(100%) 20(100%) 0

40
Table 13: FIBROMYALGIA IMPACT QUESTIONNAIRE (FIQ)
There is about 30-40 % difference in both the groups from visit 1 to visit 2 which is latter on maintained on well in group B
This shows there is remarkable difference seen in Fibromyalgia Imapct from visit 1 visit 2 which has decreased.
FIQ Group A Group B P value
Visit 1 81.90±5.81 83.80±7.01 0.357
Visit 2 50.55±9.5 49.50±9.01 0.772
Visit 3
56.85±5.95
55.05±3.86 0.263
Visit 4 57.10±3.64 58.95±6.01 0.247
Signifiacne <0.001** <0.001**

41
Table 14: Brief Pain Inventory (Short Form)
Even BPI score have reduced from visit 1 to visit 2 but here the scores are equal in both the groups.
Brief Pain
Inventory (Short
Form)
Group A Group B P value
Visit 1 83.50±1.24 83.70±1.69 0.671
Visit 2 35.65±2.94 35.40±2.62 0.788
Visit 3 44.45±2.48 44.05±1.73 0.558
Visit 4 45.35±2.03 45.00±1.56 0.545
P value <0.001** <0.001** -

42
5. DISCUSSION AND LIMITATION OF THE STUDY
There are a number of interesting points to this case. First, it demonstrates the effectiveness of
combination therapy and monotherapy in a patient suffering with fibromyalgia and it the sleep
disturbances improvement to induce sleep and reduce pain. There are not many studies conducted on
combination treatment our study first time took this combination of Etodolac and Diazeam. The
results clearly states that Combination treatment proves to be better than etodolac alone.
In the previous qualitative studies described in the literature, participants in this study expressed that
FM had a profoundly negative impact on their lives in general and their sleep in particular. Many
participants reported that since having FM, they were no longer able to experience a truly good night
of sleep that would result in feeling refreshed or rested upon awakening. Participants' responses to
general, open-ended questions regarding the impact of FM on their sleep, as well as their feedback
upon item review, provide strong evidence for the content validity of both PRO measures for
complementary purposes. Specifically, the Sleep Quality NRS was reported by participants to be
relevant and appropriate for addressing the overall impact of FM on their sleep. Furthermore,
participants stated that the overall assessment of their sleep quality facilitated by this measure was
both important and similar to the type of information they provided to their physicians about the
consequences of their nocturnal FM pain. These findings, along with the brevity, ease of use, and
daily recall period provide further support for use of the Sleep Quality NRS in both routine clinical
practice and in research studies as part of a patient diary.
Sleep medicines are generally used to treat insomnia and sleep related disorders. Many studies have
proved the sleep disorder is most commonly seen in FM patients. They find difficulty I falling asleep
hence sleep medicines are proved to be very effective the basic thing is to induce sleep improve
sleep and enhance day time functioning the drugs which are prescribed are the central nervous
system depressants Ambien (zolpidem tartrate) and Sonata (zaleplon). Prescribed for short duration
of time as it causes dependence. Recently found although not yet approved by the FDA specifically
for the treatment of fibromyalgia, the central nervous system depressant known as Xyrem is a
promising drug currently being assessed for use in individuals with FM. Because persons with
fibromyalgia have trouble falling asleep, staying asleep, or getting quality, restorative sleep, sleep
medicines have been found useful in FM management. By improving sleep, it is also possible to
decrease pain and achieve better daytime functioning. Examples of commonly prescribed drugs
include the central nervous system depressants Ambien (zolpidem tartrate) and Sonata (zaleplon).

43
These drugs can be habit-forming and are therefore usually prescribed for short periods of time. A
new product, Lunesta (eszopiclone), is one of the generation of sleep aids like Ambien which helps
people to fall asleep without the next day hangover characteristic of older-generation sleep drugs.
Lunesta is the first drug to be approved for long-term use (though others may be tested in the future),
and it helps people to stay asleep. Although not yet approved by the FDA specifically for the
treatment of fibromyalgia, the central nervous system depressant known as Xyrem is a promising
drug currently being assessed for use in individuals with FM. Clinical trials in FM patients have
already shown significant pain relief and improved functioning. Sodium oxybate, the active
ingredient of Xyrem, is a sodium salt of gammahydroxybutyrate (GHB), a substance with a history
of abuse. Therefore, Xyrem is highly controlled through a restricted distribution system
Prior evidence suggests that medication and selfmanagement approaches to care can improve
symptoms, function and well-being in this patient population. Recent studies examining the efficacy
of two serotonin and norepinephrine-reuptake inhibitors – duloxetine and milnacipran – and the
anticonvulsant pregabalin are encouraging. Studies evaluating different forms of exercise continue to
support the belief that increased physical activity is an essential component of any treatment plan for
the patient with fibromyalgia. Three studies added to the understanding of treatment adherence.
Finally, three studies evaluating the efficacy of acupuncture in the treatment of fibromyalgia showed
conflicting results, but added to the knowledge needed for clinicians to have substantive
conversations with patients.
progressive walking, simple strength training movements, and stretching activities are effective
at improving physical, emotional, and social function, key symptoms, and self-efficacy in women
with fibromyalgia who are being actively treated with medication. Furthermore, the benefits of
exercise are enhanced when combined with targeted self-management education, and
improvements in physical function continue for 6 months after completion of the intervention.

44
Limitation of this study
Much data could not be acquired from the literature of review since there are no studies still
conducted on these drugs Lack of time restricted the study outcomes. This study was also
restricted to only one site that did notrepresent the whole population. Language barrier was another
limitation.

45
6. CONCLUSION AND FUTURE WORK
The Combination treatment proves to be better in some instance whereas in other case both the
treatments are equally effective. Combination of Etodolac and Diazepam seems to be more effectively
inducing sleep and reducing pain where as when etodolac given alone reduces the pain better sleep is
not induced. Demographic data shows that females (55%) participants were more when compared with
men(45%), even the occupation shows that the house wives are affected more. The Combination group
showed improvement in the sleep disturbances hence this study proves Combination treatment then
mono treatment.
There is mean decrease in Fibromyalgia Imapct from visit 1 visit 2. Even BPI score have reduced
from visit 1 to visit 2 but here the scores are equal in both the groups. PSQI has shown remarkable
difference in both the groups Group B is quite ahead than Group A in few instances, group B has
maintained the improvement from visit 1 to follow-up 2 visit. Lowering the pain intensity
Future work:
A lot more has to be done still to improve the present condition of treatment situation of
Fibromyalgia. First of all the cause the etiology should be made clear there still lot many unclear
data about FM. Companies should focus more on it because day by day the instances of FM are
increasing due the life style changes and sedentary life. The association of FM with Sleep and Stress
need more attention by the researchers hence I would like to conclude saying that a small step today
can create a better world tomorrow.

46
7. REFERENCES
1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria
for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis
Rheum 1990; 33:160±172.
2. Henriksson C, Liedberg G. Factors of importance for work disability in women with
fibromyalgia. J Rheumatol 2000; 27:1271±1276.
3 Wolfe F, Anderson J, Harkness D, et al. A prospective, longitudinal, multicenter study of service
utilization and costs in fibromyalgia. Arthritis Rheum. 1997;40:1560-1570.
4. Gran JT. The epidemiology of chronic generalized musculoskeletal pain. Best Pract Res Clin
Rheumatol. 2003;17(4):547-561.
5. Bergman S, Herrstrom P, Hogstrom K, et al. Chronic musculoskeletal pain, prevalence rates,
and sociodemographic associations in a Swedish population study. J Rheumatol. 2001;28:1369–
1377.
6. Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. (March 2007). "An internet survey of
2,596 people with fibromyalgia.". BMC Musculoskelet Disord. 9;8:27. 9 (6): 27.
7. Russell IJ, Fletcher EM, Michalek JE, McBroom PC, Hester GG. Treatment of primary
fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam: a double-blind, placebo-
controlled study. Arthritis Rheum. 1991;34:552-560.
8. Jacobs JWG, Rasker JJ, van der Heide A, et al. Lack of correlation between the mean tender
point score and self- reported pain in fibromyalgia. Arthritis Care Res 1996; 9:105±111.
9. Stormorken H; Brosstad F (1992). "Fibromyalgia: family clustering and sensory urgency with
early onset indicate genetic predisposition and thus a "true" disease". Scand J Rheumatol. 21 (4):
207
10. Arnold LM, Hudson JI, Hess EV, et al. (March 2004). "Family study of fibromyalgia".
Arthritis Rheum. 50 (3): 944–52
11. Buskila D, Sarzi-Puttini P (2006). "Biology and therapy of fibromyalgia. Genetic aspects of
fibromyalgia syndrome". Arthritis Res Ther. 8 (5): 218
12. Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA (January 1992).
"Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with
fibromyalgia/fibrositis syndrome". J Rheumatol. 19 (1): 104–9

47
13. Sarno, Dr. John E. et al. (2006). The Divided Mind: The Epidemic of Mindbody Disorders.
New York: HC. pp. 21–2, 235–7, 294–8
14.Bernard Rosner (2000), Fundamentals of Biostatistics, 5th
Edition, Duxbury, page 80-240
15. M. Venkataswamy Reddy (2002), Statistics for Mental Health Care Research, NIMHANS
publication, INDIA, page 108-144
16.Sunder Rao P S S , Richard J(2006) : An Introduction to Biostatistics, A manual for students in
health sciences , New Delhi: Prentice hall of India. 86-160
17. Rickels K; Schweizer E, Case WG, Greenblatt DJ (October 1990). "Long-term therapeutic use
of benzodiazepines. I. Effects of abrupt discontinuation". Arch Gen Psychiatry 47 (10): 899–907
18. Chweh AY; Swinyard EA, et al (February 25, 1985). "Effect of GABA agonists on the
neurotoxicity and anticonvulsant activity of benzodiazepines". Life Sci 36 (8): 737–44
19. Diazepam". PubChem. National Institute of Health: National Library of Medicine. 2006.
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3016. Retrieved 2006-03-1
20. Goldenberg DL: Fibromyalgia syndrome a decade later: what have we learned? Arch Intern
Med 1999; 159:777–785
21. Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, et al: Gender differences in treatment
response to sertraline versus imipramine in chronic depression. Am J Psychiatry 2000;157:1445-52
22. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality
Index: A new instrument for psychiatric practice and research. Psychiatry Research 28:193-213,
1989.
23. Carette S, Bell MJ, Reynolds WJ, et al. Comparison of amitriptyline, cyclobenzaprine, and
placebo in the treatment of fibromyalgia. Arthritis Rheum 1994;37:32-40.
24. Turk DC, Meichenbaum DH. A cognitive-behavioural approach to pain management. In: Wall
PD, Melzack R, eds. Textbook of pain. Edinburgh: Churchill Livingstone, 1989:1001-9.
25. Haanen HC, Hoenderdos HT, van Romunde LK, et al. Controlled trial of hypnothrapy in the
treatment of refractory fibromyalgia. J Rheumatol 1991;18:72-5
26. Burckhardt CS, Mannerkorpi K, Hedenberg L, et al. A randomized, controlled clinical trial of
education and physical training for women with fibromyalgia. J Rheumatol 1994;21:714-20

48
27. White KP, Harth M. An analytical review of 24 controlled clinical trials for fibromyalgia
syndrome (FMS). Pain 1996;64:211-9.
28. Simms RW, Felson DT, Goldenberg DL. Criteria for response to treatment in
fibromyalgia(abstr). Arthritis Rheum 1988;31:S100
29. Linton SJ, Hellsing AL, Anderson DJ. A controlled study of the effects of an early intervention
on acute musculoskeletal pain problems. Pain 1993;54:353-9.
30. Rotter JB. Generalized expectancies for internal versus external control of reinforcement.
Psychol Monogr 1966;80:1-28.

49
APPENDICES
1. Protocol
2. Case report form
3. Informed consent form
4. Fibromyalgia Impact Questionnaire with permission letter
5. Pittsburgh Sleep Quality Index with permission letter
6. Brief Pain Inventory Questionnaire with permission letter
7. Permission letter from Dr.P.K.Raju for conducting the study at Susruta Orthopedics clinic,
Bangalore
8. Bangalore Medical College Ethics Committee approval letter
9. ACR 1990 classification criteria
10. PSQI Scoring

50
Study Protocol
The Effectiveness of Etodolac and Combination Of
Suffering
From Fibromyalgia
By: Laxmi Maurya
Roll No: s048171
Mentor: Dr.Lincy Jaison

51
Table of Contents
1. CLINICAL STUDY SUMMARY…………………………………………… 3- 4
2. INTRODUCTION……………………………………………………………… 4
3. STUDY OBJECTIVES………………………………………………………… 5
3.1 PRIMARYOBJECTIVES
3.2 SECONDARY OBJECTIVES
4. STUDY DESIGN………………………………………………………………. 5
5. PATIENT SELECTION....…………………………………………………….. 5
5.1 INCLUSION CRITERIA
5.2 EXCLUSION CRITERIA
6. RANDOMIZATION …………………………………………………………….. 5
7. TREATMENT …………………………………………………………………… 6
8. INVESTIGATIONS / PROCEDURES ....……………………………………… 6
9. ADVERSE EVENTS ……………………………………………………………. 6
10. DISCONTINUATION OF STUDY ……………………………………………. 6
11. FOLLOW-UP OF PATIENTS ………………………………………………… 7
12. STATISTICS …………………………………………………………………… 7
13. MONITORING …………………………………………………………………. 7
14. QUALITY CONTROL AND QUALITY ASSURANCE ……………………. 7
15. ETHICS …………………………………………………………………………. 7
16. DATA HANDLING AND RECORD KEEPING ……………………………… 7
17. REFERENCES ………………………………………………………………… 8

52
CLINICAL TRIAL SUMMARY:
TITLE A single centre, Randomized, parallel group, interventional pilot
study to compare the effectiveness of Etodolac alone and
Combination of Etodolac with Diazepam in Patients suffering
from Fibromyalgia.
INVESTIGATOR
Co-INVESTIGATOR
TRIAL LOCATION
Dr. P.K.Raju
Laxmi Maurya
Sushruta Orthopaedic Centre / Bangalore/ India.
STUDY DESIGN This is a single centre, randomized, interventional- prospective
pilot study with two groups. Where
Patients will be randomly assigned to receive either Etodolac or
Combination of Etodolac & Diazepam for 10 days.
STUDY POPULATION
Inclusion criteria:
 Patients Diagnosed of Fibromyalgia according to the
American College of Rheumatology Criteria.
 Newly Diagnosed Fibromyalgia Patients < 3months.
 Pain intensity marked on VAS greater or equal to 4 (on 0
-10 scale)
 Both gender
 Age 18 to 65
 Literate person, who can understand and comply with the
requirements of the study.
Exclusion criteria:  Patient unwilling to give informed consent.
 If pain is not primarily due to Fibromyalgia.
 Pregnant or nursing mother.
 Patient with any other chronic conditions.
 Participation in other therapeutic trials.
 Had diazepam 1 week before the study or suggested
physiotherapy.
 Patient working in night shift (11PM - 7AM).
 Patient diagnosed with sleep disorder earlier.
 Patient undergoing any complementary therapy.

53
Total expected number of patients:
MEDICATION TO BE GIVEN
Route of administration:
Dose regimen:
Total number of patients to be recruited = 20 in each group.
Group A = 20 will be given medication Etodolac alone.
Group B = 20 will be given medication (diazepam + Etodolac).
Diazepam and Etodolac will be given orally with water.
Group A: 400 mg Tab Etodolac will be given for 10 days
continuously every night before going to bed.
Group B: 5 mg Tab diazepam and 400 mg Tab Etodolac every
night for 10 days before going to bed.
PRIMARY OBJECTIVE:
SECONDARY OBJECTIVES:
To find out which treatment is more effective, Etodolac alone or
Etodolac when combined with diazepam.
2. To find out Improvement in sleep disturbances in
fibromyalgia patients by taking diazepam.
3. To find out how many patients require continuation of
medication after the 10th
day of the treatment.
ENDPOINTS
Primary End Point:
Secondary End Points:
DURATION OF STUDY PERIOD
Questionnaires administered :
 Decrease from Baseline to End points In the Total Score
of Fibromyalgia Impact Questionnaire.
Time Frame: baseline, 10th
, 20th
, & 30th
day of the treatment
 Decrease from baseline to end points in the total score of
Pittsburgh sleep quality index and in the total score of
Brief Pain Inventory.
Time Frame: baseline, 10th
, 20th
, & 30th
day of the treatment.
.
30 days divided into two phases = 10days for treatment
+ 20 days for follow up.
 VAS to measure Pain Intensity
 Fibromyalgia Impact Score (FIQ)
 Brief Pain Inventory
 Pittsburgh sleep quality index.

54
2. Introduction
Fibromyalgia is commonly found causing muscle pain and tenderness in muscles at several parts of
the body that is neck, shoulders, back and hips. It is known as chronic disorder where the patient
feels the pain even if slightly pressed at the tender area.
It is said other then pain and fatigue, fibrmyalgia patients may experience sleep disturbances. The
reason to conduct this study is to find out, which is more effective in giving relief to the patients
suffering from fibromyagia, Etodolac or combination of etodolac and diazepam and Induce better
sleep in patients by giving diazepam.
Drug:
Diazepam first marketed as Valium by Hoffmann- La Roche is a benzodiazepine derivative drug. It
possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic
properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, alcohol
withdrawal.
Etodolac commercially known as Lodine (etodolac) Etodolac is a non steroidal anti-inflammatory
drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models.
The mechanism of action of etodolac, like that of other NSAIDs, is not known but is believed to be
associated with the inhibition of prostaglandin biosynthesis.
3. Study Objectives
Primary objective:
To compare the effectiveness of Etodolac or a combination of Etodolac + diazepam in treating
patients suffering from Fibromyalgia
Secondary objectives:
4. Study Design
This is a single centric trial the study will be held in Sushruta Orthopaedic Centre in Bangalore; A
prospective-interventional pilot study with two groups undergoing two different treatments
simultaneously. Randomization will be done to assign treatment group and to avoid any kind of bias.
2. To find out Improvement in sleep disturbances in fibromyalgia patients by taking diazepam.
3. To find out how many patients require continuation of medication after the 10th
day of the
treatment.

55
5. Patient selection:
Inclusion criteria:
 Patients Diagnosed of Fibromyalgia according to the American College of Rheumatology
Criteria.
 Newly Diagnosed Fibromyalgia Patients < 3 months time.
 Pain intensity marked on VAS greater or equal to 4 (on 0 -10 scale)
 Both gender
 Age 18 to 65
 Literate person, who can understand and comply with the requirements of the study.
Exclusion criteria:
 Patient unwilling to give informed consent.
 If pain is NOT primarily due to Fibromyalgia.
 Had diazepam 1 week before the study or suggested physiotherapy.
 Patient undergoing any complementary therapy.
6. Randomization
On enrolling in the study, a patient receives a subject number and according to which treatment
group will be sequentially allotted after randomization.
Randomization is done in 1: 1 ratio after the enrollment of the patients for both treatment group’s
medication and non drug therapy respectively for 10 days acute treatment.
7. Treatment
Group A: Etodolac (400 mg) given for 10 days once at night times before sleep.
Group B: Etodolac (400 mg) and Diazepam tablets (5 mg) given orally once daily at night times.
To be stored in dark and cool place, do not expose to direct sunlight and moist places.
8.Investigations/Procedures
This study is designed to assess and compare the effectiveness of treatment Etodolac alone with
combination treatment of Etodolac and Diazepam hence, it is randomized to avoid any kind of bias.

56
After screening & enrollment, randomization will be done. Patients will be provided with patient
number and group of the treatment once randomization is done, where
Group A will be given orally 400 mg Tab Etodolac for 10 days consecutively every night before
going to bed.
Group B will be given Tab Diazepam orally 5 mg and Tab Etodolac (400mg) every night before
going to bed for 10 days.
Questionnaires will be administered to the patients after randomization, which will be at baseline
then, at the end of treatment (Day 10), & at Follow up visits (Day 20 & 30)
To find out efficacy patient will be administered questionnaires:
 Visual analogue scale from 0 to 10, where 0= no pain and 10= worst pain.
 Fibromyalgia Impact Questionnaire (FIQ)
 Pittsburgh Sleep quality Index (PSQI).
 The Brief pain Inventory.
Time Frame:
Treatment Time Frame For : Group A or
Group B
Day 0
Screening, Enrollment and randomization
Only VAS Score Administered
Week 1
Start of Treatment Visit 1 either group A or Group B: Day 1
Week 2
End of Treatment Visit 2: Day 10
Week 3
Follow-up Visit1: Day 20
Week 4
Follow-up Visit 2: Day28 +/- 2 days.

57
9. Adverse events
Development of tolerance to the sedative effects is usually seen during the course of therapy,
Information of the adverse events (if any) will be collected from the patients from the date of
informed consent signature until the closure of the study.
10. Discontinuation of the study
Temporary treatment discontinuation may be considered by the investigator because of suspected
Adverse Drug Reactions. The patients may withdraw from trial at any time and irrespective of the
reason.
Study treatment will be stopped if any of the following events occur:
 No post baseline efficacy data
 Premature withdrawal
 Insufficient compliance
 Protocol violation.
11. Follow up of patients
There will be two follow-up visits after the 10 days of acute treatment. The gap between the two
visits will be 10 days and in each visit questionnaire will be administered to the patients.
12. Statistics
Data will be analyzed by the Wilcoxon signed-rank test, Rank-sum test and t-test
13. Monitoring
This study will be monitored by the ethics committee and at regular interval of times updating will
be done. The adverse event updation will be given to ethics committee if occurs any at the site.
14. Quality control and Quality assurance
The investigator will maintain the quality during the trial. It’s his duty to take all necessary steps to
ensure proper conduct of the study with compliance to protocol.
Ethics committee will also look into the monitoring of the study.
15. Ethics

58
The clinical study will be conducted according to Declaration of Helsinki and all amendments made
by the World Medical Assembly and for Good Clinical Practice ICH guidelines to be followed.
This clinical trial will be conducted keeping in mind national regulation and laws.
Submission of protocol by to the ethics committee for the initiation of the study without the approval
of the ethics study cannot be started by the investigator or the sponsor at site. The submission
includes protocol, informed consent and Questionnaires.
16. Data handling and storage
Monitor will check the entries of the case repot form entries maintain ICH guidelines for Good
Clinical Practice. Confidentiality should be maintained all the time during the trial by the
investigator. Investigator should retain study documents for at least 15 years after the completion of
the study in a safe place.
17. References
1. Cedraschi, C., Desmeules, J., Rapiti, E., Baumgartner, E., Cohen, P., Finckh, A., Allaz, A. F.
and Vischer, T. L. (2004), “ Fibromyalgia a randomized controlled trial of a treatment
programme based on self management”. Annals Rheumatology Disease, vol. 63, pp. 290–
296.
2. Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R. and Kupfer, D. J. (1989), “The
Pittsburgh Sleep Quality Index: a new instrument For Psychiatric Practice and Research”.
Elsevier Scientific Publishers Ireland Ltd, vol. 0165, pp. 1781/89.
3. Leventhal, L. J. (1999), “Management of Fibromyalgia”. Annals of Internal Medicine, vol.
131 no. 11, pp. 850-858.
4. Bennett, R. (2005), “The Fibromyalgia Impact Questionnaire (FIQ): a review of its
development, current version, operating characteristics and uses”, Clin Exp Rheumatology,
vol. 23, pp. S154-S162.
5. Wolfe, F., Smyth. H. A., Yunus. M. B. (1990). “The American College of Rheumatology
1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria
Committee”, Arthritis Rheum, vol. 33, pp. 160-72.

59
CASE REPORT FORM
Patient Demographic Details Date: __/__/__
Patient Name: _________ Date of Birth: __/__/__
Age: _____
Sex: Male/ Female
Marital Status:
Single/ Married/ Widow/ divorced
Religion: Hindu / Muslim/ Christian / Others
Literacy:
1. __ Literate
2. __ Graduate
3. __ Post-Graduate/ Professional degree
Occupations (specify titles; if you are not working, tell us your previous occupation):
_________________________________________________________________________
How long has it been since you first learned your diagnosis?
__Days / month
Please use this pain assessment scale to fill out your pain intensity.
0 1 2 3 4 5 6 7 8 9 10
No Pain Worst pain

60
INFORMED CONSENT FORM
Dear Participant,
You are invited to participate in a study going to be conducted by me, Laxmi Maurya student of
M.Sc. Clinical research, Institute of clinical research India.
You are selected as the potential participants for this study because you are diagnosed with
Fibromyalgia according to the American College of Rheumatology Criteria.
This study is to find out which treatment is more effective one of the treatment is Etodolac given
orally and the other treatment is Etodolac + diazepam given orally. There will be no bias in
allocating the treatment groups as patients will be randomized in this study. Patient need to fill in
few questionnaires based on which we will find out the results. It is a 30 days study where for 10
days treatment will be given and for next 20 days follow-up.
If you decide to participate, we will take your data like your medical history and your personal data
such as age, sex, religion etc. Following questionnaires will be administered
 VAS to measure Pain Intensity
 Fibromyalgia Impact Score (FIQ)
 Brief Pain Inventory
 Pittsburgh sleep quality Index (PSQI). .
There is no risk and discomfort involved as you will be given only medication to relief you from
pain. This study does provide direct benefit to the participants. This study will help us to find the
better and effective treatments for the patients having fibromyalgia.
You cannot be in this study if any of the following apply to you
 Patient unwilling to give informed consent.
 If pain is NOT primarily due to Fibromyalgia.

61
 Had diazepam 1 week before or suggested physiotherapy.
 Patient undergoing any complimentary therapy.
Your personal health information (PHI) will be kept private to the extent allowed by law. Any
information that is obtained in connection with this study and that can be identified with you will
remain confidential and will be disclosed only with your permission. Your data will be used by The
Doctor P.K.Raju by me Laxmi Maurya and my mentor Dr. Lincy for academic and research purpose
only.
Your decision to participate in this study is voluntary. Your decision whether or not to participate
will not prejudice your future relation with the doctor. If you decide to participate, you are free to
discontinue participation at any time without prejudice.
If you have any questions, please do not hesitate to contact me. If you have any additional question
questions later, please contact me at lxmmaurya@gmail.com and 9986472030, we will be happy to
answer them.
You will be offered a copy of this form to keep.
You are making a decision whether or not to participate. Your signature indicates that you have read
the information provided above and have decided to participate. You may withdraw at any time after
signing this form.
Signature Date

62
Informed consent form to participate in a clinical trial
Study title: A randomized pilot study to compare the effectiveness of etodolac alone and etodolac
compared with diazepam in treating the patients suffering from fibromyalgia.
Subject’s initial: _____________________
Subject’s name: ______________________
Date of birth/ Age: ___________________
1. I confirm that I have read and understood the information sheet dated________ for the above
study and have had the opportunity to ask questions. [ ]
2. I understand that my participation in the study is voluntary and that I am free to withdraw at any
time, without giving any reason, without my medical care or legal rights being affected. [ ]
3. I understand that the sponsor of the study, others working on the sponsor’s behalf, the ethics
committee and the regulatory authorities will not need my permission to look at my health records
both in respect to the current study and any further research that may be conducted in relation to it,
even if I withdraw from the study. I agree to this access. However, I understand that my identity will
not be revealed in any information released to third parties or published. [ ]
4. I agree not to restrict the use of any data or results that arise from the study provided such a use is
only for scientific purpose(s). [ ]
5. I agree to take part in the above study. [ ]
6. I agree my identity can be disclosed under the orders of constitution of law. [ ]
1. Signature (or thumb impression) of the subject / Legally Acceptable Representative:
______________________________ Date: _ _/___/_____
Signatory’s Name: _____________________________________________________
2. Impartial Witness: _____________________________ Date: _ _/___/_____
Signatory’s Name
_____________________________________________________

63
1990 Criteria for the Classification of Fibromyalgia
1. History of widespread pain.
Definition. Pain is considered widespread when all of the following are present: pain in the left side of
the body, pain in the right side of the body, pain above the waist, and pain below the waist. In
addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be
present. In this definition, shoulder and buttock pain is considered as pain for each involved side.
"Low back" pain is considered lower segment pain.
2. Pain in 11 of 18 tender point sites on digital palpation.
Definition. Pain, on digital palpation, must be present in at least 11 of the following 18 sites:
Occiput: Bilateral, at the suboccipital muscle insertions.
Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5-C7.
Trapezius: Bilateral, at the midpoint of the upper border.
Supraspinatus: Bilateral, at origins, above the scapula spine near the medial border.
Second rib: Bilateral, at he second costochondral junctions, just lateral to the junctions on upper
surfaces.
Lateral epicondyle: Bilateral, 2 cm distal to the epicondyles.
Gluteal: Bilateral, in upper outer quadrants of buttocks in anterior fold of muscle.
Greater trochanter: Bilateral, posterior to the trochanteric prominence.
Knee: Bilateral, at the medial fat pad proximal to the joint line.
Digital palpation should be performed with an approximate force of 4 kg.
For a tender point to be considered "positive" the subject must state that the palpation was painful.
"Tender is not to be considered "painful."
* For classification purposes, patients will be said to have fibromyalgia if both criteria are satisfied.
Widespread pain must have been present for at least 3 months. The presence of a second clinical
disorder does not exclude the diagnosis of fibromyalgia.

64
Pittsburgh Sleep Quality Index (PSQI)
References and Scoring
Reference
Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: A new
instrument for psychiatric practice and research. Psychiatry Research 28:193-213, 1989.
Notes on data entry
The range of values for questions 5 through 10 are all 0 to 3.
Questions 1 through 9 are not allowed to be missing except as noted below. If these questions are
missing then any scores calculated using missing questions are also missing. Thus it is important to
make sure that all questions 1 through 9 have been answered.
In the event that a range is given for an answer (for example, ‘30 to 60’ is written as the answer to Q2,
minutes to fall asleep), split the difference and enter 45.
Scores – reportable in publications
On May 20, 2005, on the instruction of Dr. Daniel J. Buysse, the scoring of the PSQI was changed to set
the score for Q5J to 0 if either the comment or the value was missing. This may reduce the DURAT score
by 1 point and the PSQI Total Score by 1 point.
PSQIDURAT DURATION OF SLEEP
IF Q4 > 7, THEN set value to 0
IF Q4 < 7 and > 6, THEN set value to 1
IF Q4 < 6 and > 5, THEN set value to 2
IF Q4 < 5, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIDISTB SLEEP DISTURBANCE
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF Q5JCOM is null
or Q5j is null, set the value of Q5j to 0) = 0, THEN set value to 0
or Q5j is null, set the value of Q5j to 0) > 1 and < 9, THEN set value to 1
or Q5j is null, set the value of Q5j to 0) > 9 and < 18, THEN set value to 2
or Q5j is null, set the value of Q5j to 0) > 18, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQILATEN SLEEP LATENCY
IF Q5a + Q2 = 0, THEN set value to 0
Field recoded: IF Q2 > 0 and < 15, THEN set value to 0
IF Q2 > 15 and < 30, THEN set value to 1
IF Q2 > 30 and < 60, THEN set value to 2
IF Q2 > 60, THEN set value to 3)

S048171_MARYA_THESIS

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S048171_MARYA_THESIS