Top Rated Bangalore Call Girls Mg Road ⟟ 9332606886 ⟟ Call Me For Genuine S...
Pediatric Vasculitis Initiative (PedVas) A CIHR Emerging Team Grant in Rare Disease (2012)
1. Pediatric Vasculitis Initiative (PedVas)
Update for CORD Rare Disease Conference,
March 2015
Susa Benseler, MD PhD
Chief Rheumatology, Alberta Children’s Hospital
on behalf of
David Cabral
Dirk Foell
Jinko Graham
Bob Hancock
Raashid Luqmani
Colin Ross
International childhood vasculitis investigators
contributing to ARChiVe, BrainWorks & DCVAS
A CIHR Emerging Team Grant in Rare Disease (2012)
2. Pediatric Vasculitis Initiative (PedVas)
• CIHR- , Vasculitis foundation and CORD-
supported opportunity to support existing
clinical childhood vasculitis networks with a
translational research component involving
collection & analysis of biological samples and
Knowledge Translation
• International & multi-disciplinary collaboration
between bench scientists and clinicians
3.
4. 9 year old girl
• ER: presented with weeks of fever on and off,
fatigue, congestion, swollen glands,
nosebleeds and cough
• Previously perfectly healthy
5. Laboratory test results
• High levels of inflammatory markers
• No evidence of infection
• Positive ANCA antibodies
9. 6 year old girl
• For 2 weeks complaining
of nausea, headaches,
mood changes, school
concentration difficulties
• ? Virus infection
(pediatrician)
• ER: blood work and CT
normal
10. • Perfectly health in the past medical history
• No travel, no infection, no injury
6 year old girl
11. Laboratory test results
• High levels of inflammatory markers
• No evidence of brain infection or bleed
• Spinal tap: inflammation/irritation
12. Acute worsening
• Vomiting, headache,
• Decreased level of
conciousness,
• neck stiffness
• Seizure status
• No fever, no other
symptoms
16. Questions asked by families and
health care providers
• What is childhood vasculitis?
• What caused it? Are siblings at risk?
• How to best make the diagnosis and avoid
invasive tests?
• Is there a cure?
• Which treatment to choose? Are the
treatments dangerous?
• How will this affect her future?
17. A registry for childhood systemic vasculitis
• 40 US/Canadian centers
• Launched 2008
A prospective registry for CNS vasculitis
• 210 centers around the word
• Launched 2010
Building international networks…
David Cabral and Susa Benseler
18. • Approach: Learn from each and every child
• Web-based, password secured
prospective data collections that connect
physicians of many disciplines around the world
• Provides treatment protocols, SOPs, review
scales, outcome tools, literature updates and
second opinions
• Publications, advocacy, data ownership rule
30. Questions asked by families and
health care providers
• What is childhood vasculitis?
• What caused it? Are siblings at risk?
• How to best make the diagnosis and avoid
invasive tests?
• Which treatment to choose? Are the
treatments dangerous?
• How will this affect her future?
• Is there a cure?
35. Questions asked by families and
health care providers
• What is childhood vasculitis?
• What caused it? Are her siblings at risk?
• How to best make the diagnosis and avoid
invasive tests?
• Which treatment to choose? Are the
treatments dangerous?
• How will this affect her future?
• Is there a cure?
40. Canadian Neuropathology study
• Neuropathologists across Canada, external
experts including Harry Vinters, lead: Cynthia
Hawkins
• Tasks:
– development and validation of a Brain Biopsy Review
Tool for Childhood CNS vasculitis
– Defining childhood CNS vasculitis histologically
Tool development completed, RedCap version
Validation: 50 biopsies (cPACNS, other IBrainD,
epilepsy surgery specimens)
• Consensus meeting, Manuscripts in preparation
41. Towards a histological diagnosis of cPACNS
30 SVcPACNS cases
10 epilepsy controls
10 inflammatory controls
42. Questions asked by families and
health care providers
• What is childhood vasculitis?
• What caused it? Are her siblings at risk?
• How to best make the diagnosis and avoid
invasive tests?
• Is there a cure?
• Which treatment to choose? Are the
treatments dangerous?
• How will this affect her future?
63. • Assessing pediatric phenotype & outcomes.
• Assessing, developing clinical tools (classification,
severity, activity, damage) & treatment protocols
to help physicians
• Embedded comparative study with adults & DCVAS
• Re-evaluating ‘classification’ using
bioinformatics to evaluate clinical data with
linked gene expression profiles.
• Biomarker discovery
PedVas
64. Current Status
Site recruitment
– 48 sites from 10 countries collecting clinical data
– 21 sites from 7 countries with ethics for biosampling
Clinical data
– 381 systemic vasculitis patients
– 228 primary CNS vasculitis patients
(Approx 90% have follow-up data up to 12 months)
Biological samples
– 93 patients contributed (RNA, DNA, serum, plasma, urine)
• First adult (DCVAS) samples collected in Aug ’14
• Abstracts 5, manuscripts: 4 published, 3 in preparation
66. Challenges
Difficulties in cIinical data versus biosamples!
• ethics approval challenges for blood collection and
shipping across borders
• contract negotiations between universities because
funding is being provided
• workload (& costs) for bio-sampling and shipping
• Some countries sites prohibit release of biosamples
Study start-up activities taking up to 12 months per site
(ethics approval, contract negotiation, laboratory set-up, training)
67. Site Initiation Timeline
New site or
Existing ARChiVe/
Brainworks site
Ethics amendment or
Brand new application
Agreements Review
-Funds Transfer Letter
- Material Transfer
Agreement (if required)
- UBC UILO Office
- Site Legal Office
• Time to ethics approval: 10 months
(Ranges 2 - 19 m (some pending for > 20 months)
• Time to fully signed agreement: 4 months
(Ranges 1 to 8 m (some pending for > 13 months)
Average
time:
4 months
Average
time:
10 months
Site Study Start-up
- Laboratory Set-up
- Site Initiation
Call/Training
- Database access
- Supplies mailed
Recruitment!
Approx
1 month
Approx
1 month
68. Preliminary Data:
Early outcomes in pediatric systemic vasculitis
Morishita K, et al at ACR Boston 2014
• 79 children: 6- and 12-month outcomes
• Primary findings:
– Majority had severe disease with kidney failure and lung bleeds
disease
– Only half achieved remission by 6 months
– Only two thirds achieved remission by 12 months
– One in two children relapses
– A significant proportion of patients have evidence of damage
even by 12 months
69. Preliminary Data:
S100 A12 Biomarkers
S100A12 measured healthy
people and children with
vasculitis
Serum S100A12 levels are
highest at the time of diagnosis
when vasculitis is most active.
(More sensitive than ESR & CRP)
Levels decline after treatment,
but rarely reaches levels
measured in serum from healthy
individuals