PedVas: Pediatric Vasculitis Initiative

Sponsor

University of British Columbia (Other)

Overall Status

Recruiting

CT.gov ID

NCT02006134

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), Simon Fraser University (Other), Child and Family Research Institute (Other), Alberta Children's Hospital (Other), University Hospital Muenster (Other), The Hospital for Sick Children (Other), University of Oxford (Other)

1,600

Enrollment

Locations

109.9

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Childhood chronic vasculitis describes a group of rare life-threatening diseases that have in common inflammation of blood vessels in vital organs such as kidneys, lungs and brain. Most knowledge about them comes from adult patients. Severe disease requires aggressive life-saving treatments with steroids and some cancer drugs which can themselves cause damage, and increase risks of cancer and severe infections. Conversely, milder disease can be treated with less toxic drugs. Different classification and "scoring tools" are used to define the types and severity of vasculitis and to measure damage caused by disease or drugs. These in turn help direct how aggressively to treat a patient and to measure outcome. None of these tools however have been assessed in children and the best balance of disease and treatment risks against outcome for children is not known. Although causes of these diseases in children and adults are probably the same, the effects of the disease and the response (good and bad) to drugs will differ in growing children. Because specialists may see only one new child with vasculitis each year, obtaining enough information to learn about childhood vasculitis requires cooperation. We will use an international web-based registry to which doctors from 50 or more centers can contribute patient data. We will determine the features which help better classify and diagnose children compared to adults. Through the web we will collect and analyze information on patients similarly classified and "scored" so that most successful treatments can be identified. Children with vasculitis are less likely to have diseases associated with aging, alcohol and smoking etc., and therefore may be a better group in whom to study the underlying biology of vasculitis. We will use this opportunity and collect spit, blood and tissue from registry patients for laboratory study with an aim to find biomarkers to better classify, define and direct optimal treatment and outcomes.

Condition or Disease	Intervention/Treatment	Phase
Wegeners Granulomatosis (Granulomatosis With Polyangiitis) Microscopic Polyangiitis Churg Strauss Syndrome (Eosinophilic Granulomatosis With Polyangiitis) Polyarteritis Nodosa Takayasu Arteritis Primary CNS Vasculitis Unclassified Vasculitis

Detailed Description

Over a 3-year period, we anticipate enrollment and collection of clinical data from as many as 600 children with various forms of childhood vasculitis, with approximately one third (200) of those children also contributing biological samples for study.

For children with vasculitis who are enrolled in the study, clinical information will be obtained from the medical chart from the time of diagnosis, post-induction (3-6 months post diagnosis) visit, 12-month clinic visit, and their most recent clinic visit or last clinic visit before discharge to adult care (ie. final outcome visit). Information that will be collected includes laboratory test results, biopsy and imaging results, disease activity, clinical history, and medications. Blood, urine, and saliva samples will also be collected at each clinic visit. If the subject experiences a disease flare, clinical data and biological samples will be collected at the time of the flare and at a later date when the disease remits.

The PedVas study is linked to an adult vasculitis initiative called DCVAS: Diagnosis and Classification Criteria in Vasculitis. Our DCVAS co-investigators and collaborators will recruit up to 250 adults at or near the time of diagnosis of the following forms of vasculitis: GPA, MPA, EGPA, TA, and UCV. Clinical data will be collected as part of the DCVAS study; this includes information such as laboratory test results, disease activity, and clinical history. Blood will also be collected and analyzed in parallel with samples collected from children with vasculitis. Finally, a DNA-biobank will be created and will house samples from approximately 700 adults and representing all forms of vasculitis. Recruitment will proceed according to DCVAS approved protocols and it will be conducted at participating DCVAS centres after the patient has formally consented to participation in the DCVAS study.

Healthy volunteers from the community will be recruited to participate in this study by word of mouth and recruitment posters. Participation for children involves a one-time donation of blood and a urine sample, while adults may donate blood and urine up to 4 times over the course of 18 months.

All biological samples will be processed and analyzed in Vancouver at the Child and Family Research Institute and at the University of British Columbia. Detailed data will be collected in electronic format and include demographic variables, socioeconomic status, detailed clinical history & physical findings, anthropometric measures, and measures of disease activity. All data for systemic vasculitis patients will be directly entered at each site into a secure, online, web-based data entry system called REDCap which is managed through the data management centre at the University of British Columbia in Vancouver. All CNS vasculitis data will be entered into the Brainworks database which is managed by the data management team at the Hospital for Sick Kids in Toronto.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1600 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Chronic Childhood Vasculitis: Characterizing the Individual Rare Diseases to Improve Patient Outcomes

Study Start Date :

Jan 1, 2013

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
PEDIATRIC VASCULITIS/PROSPECTIVE Pediatric patients in this cohort are those diagnosed with vasculitis within 12 months from study entry. Clinical data, blood (RNA, plasma, serum), urine, and saliva (DNA) will be collected at 3 to 5 timepoints: time-of-diagnosis, post-induction, 12-month post diagnosis, disease flare, and remission/post-flare.
PEDIATRIC VASCULITIS/RETROSPECTIVE Patients in this cohort are those diagnosed with vasculitis more than 12 months from study entry and/or were previously enrolled in the ARChiVe or Brainworks registries. Clinical outcome data will be collected retrospectively. Blood (RNA & serum), urine, and saliva (DNA) will be collected at 2 timepoints: disease flare, and remission/post-flare.
ADULT VASCULITIS/ COHORT 1 Adult patients in this cohort are those at or near the time of diagnosis of GPA, MPA, EGPA or unclassified vasculitis that are participants in DCVAS. Clinical data and blood (RNA, DNA) will be collected at the time-of-diagnosis only.
ADULT VASCULITIS / COHORT 2 Adult patients in this cohort are those individuals that are participants in DCVAS and have any form of vasculitis. Clinical data and blood (DNA) collected at the time-of-diagnosis will be used for study.
HEALTHY CHILDREN / PEDIATRIC CONTROL Participants in this cohort are otherwise healthy children with no history of inflammatory disease. Children will provide a one time donation of blood (RNA, serum) and urine.
HEALTHY ADULTS / ADULT CONTROL Participants in this cohort are otherwise healthy adults with no history of inflammatory disease. Adults will provide a one time donation urine and will provide blood (RNA, serum) as many as 4 times.

Outcome Measures

Primary Outcome Measures

Develop new benchmarks for outcome in pediatric patients with systemic or CNS vasculitis [within 3 yrs]
Specific and generic disease assessment tools will be used to analyze our registry cohorts to enable the first-ever benchmarks of outcome in children with GPA or PACNS who have had a minimum of 12 months follow up.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria for vasculitis subjects:

Diagnosed with ANCA-associated vasculitis (AAV: such as Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA)), Primary Angiitis of the Central Nervous System (PACNS), Unclassified vasculitis, Takayasu's Arteritis (TA) or Polyarteritis Nodosa (PAN) before age 18

Inclusion criteria for healthy controls:

Healthy adult or child

Exclusion Criteria for vasculitis subjects:

Diagnosed with other vasculitis subtypes not listed above
More than 20 years of age

Exclusion criteria for healthy controls:

Donated greater than 20 ml of blood in the previous three weeks
Has an immune disorder or blood borne infectious diseases (such as HIV or Hepatitis)
Has vasculitis, multiple sclerosis, diabetes, an autoimmune disease, a thyroid condition, or other chronic conditions involving the heart, lungs, gut or kidney
Has a previous history of anaemia or abnormal blood clotting
Has a current or previous drug abuse problem

Contacts and Locations

Locations

	Site	City	State	Country
1	University of San Francisco	San Francisco	California	United States
2	University of Florida	Gainesville	Florida	United States
3	Medical College of Georgia	Augusta	Georgia	United States
4	Comer Children's Hospital	Chicago	Illinois	United States
5	Riley Hospital for Children	Indianapolis	Indiana	United States
6	University of Louisville	Louisville	Kentucky	United States
7	The Joseph M. Sanzari Children's Hospital	Hackensack	New Jersey	United States
8	Children's Hospital at Montefiore	Bronx	New York	United States
9	Akron Children's Hospital	Akron	Ohio	United States
10	Texas Children's Hospital	Houston	Texas	United States
11	University of Utah / Primary Children's Hospital	Salt Lake City	Utah	United States
12	Seattle Children's Hospital	Seattle	Washington	United States
13	Hospital de Pediatría Garrahan	Buenos Aires		Argentina
14	University of Calgary / Alberta Children's Hospital	Calgary	Alberta	Canada
15	BC Children's Hospital	Vancouver	British Columbia	Canada
16	Janeway Childrens Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador	Canada
17	IIWK Health Centre	Halifax	Nova Scotia	Canada
18	London Health Sciences Centre	London	Ontario	Canada
19	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada
20	Hospital for Sick Children	Toronto	Ontario	Canada
21	Royal University Hospital	Saskatoon	Saskatchewan	Canada
22	Rigshospitalet	Copenhagen		Denmark
23	University Children's Hospital	Munster		Germany
24	Sanjay Gandhi Post Graduate Institute	Lucknow		India
25	Meyer Children's Hospital of Florence	Florence		Italy
26	Instituto Nacional de Pediatria	Coyoacán		Mexico
27	Saint-Petersburg State Pediatric Medical University	Saint Petersburg		Russian Federation
28	Mother and Child Health Care Institute of Serbia	Belgrade		Serbia
29	Hospital Sant Joan de Deu	Barcelona		Spain
30	Siriraj Hospital	Bangkok		Thailand
31	Birmingham Children's Hospital NHS Foundation Trust	Birmingham		United Kingdom
32	Royal Hospital for Children	Glasgow		United Kingdom
33	Leeds Children's Hospital	Leeds		United Kingdom
34	Alder Hey Children's Hospital	Liverpool		United Kingdom
35	Royal Manchester Children's Hospital	Manchester		United Kingdom
36	Great North Children's Hospital	Newcastle upon Tyne		United Kingdom
37	Nottingham Children's Hospital	Nottingham		United Kingdom
38	Nuffield Orthopaedic Centre	Oxford		United Kingdom
39	Sheffield Children's Foundation Trust	Sheffield		United Kingdom
40	Southampton General Hospital	Southampton		United Kingdom

Investigators

Principal Investigator: David Cabral, MBBS, University of British Columbia; BC Children's Hospital
Principal Investigator: Susanne Benseler, MD, PhD, Alberta Children's Hospital
Principal Investigator: Raashid Luqmani, DM FRCP(E), University of Oxford
Principal Investigator: Dirk Foell, MD, University of Muenster
Principal Investigator: Robert Hancock, PhD, University of British Columbia
Principal Investigator: Colin Ross, PhD, University of British Columbia
Principal Investigator: Jinko Graham, PhD, Simon Fraser University