Safety and Efficacy of Measles, Mumps, Rubella Vaccination in Juvenile Idiopathic Arthritis (VAART)
Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine
Background:
The safety of vaccination in patients with autoimmune diseases using immune suppressive therapy is often discussed. Previous studies in Juvenile Idiopathic Arthritis (JIA) patients showed no increase in disease activity after immunisation with dead vaccines. The safety of the live attenuated Measles, Mumps, Rubella (MMR) vaccination was assessed retrospectively in JIA patients and no increase in disease activity was found. However, this must be prospectively confirmed. In addition, it is unknown whether vaccination is effective, since the immune response to vaccination may be diminished due to immunosuppressive therapy for the underlying disease. Finally, the influence of MMR vaccination on the immune system of JIA patients has not been studied. Among others, regulatory T-cells (Tregs) should control the immune response and prevent destructive autoimmune responses after environmental triggers such as vaccination.
Objective:
The aim of the present study is to investigate the safety and efficacy of the MMR booster vaccination and its influence on immune regulatory mechanisms in children with Juvenile Idiopathic Arthritis.
Method:
JIA patients aged 4 to 8 years and treated by the pediatric rheumatology units from various University Medical Centers in the Netherlands, are asked to participate in a prospective study. In the Netherlands, measles-mumps-rubella (MMR) vaccination is included in the National Vaccination Program and is normally administered at age 9. Included patients will be randomised for early vaccination (age group 4 to 8yr at entry of the study) or at age 9 as is routinely done according to the National Vaccination Program. Prior to and after vaccination the investigators will assess disease activity and collect blood.
Outcome:
During a 12 month follow-up period the investigators will register disease activity and side-effects at different moments in time to determine safety of vaccination. The efficacy of the vaccine will be studied according to antibody levels and function against measles, mumps and rubella in the blood. Tregs will be isolated and their functionality will be determined using the blood cells collected during follow-up. This enables us to study the role influence of vaccination on regulatory mechanisms in our immune system.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Amsterdam, Netherlands, 1007 MB
- VU University Medical Center Amsterdam
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Groningen, Netherlands, 9700 RB
- University Medical Center Groningen, Beatrix Children's hospital
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Rotterdam, Netherlands, 3000 CB
- Erasmus Medical Center Rotterdam; sophia Children's Hospital
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Utrecht, Netherlands, 3508 AB
- University Medical Center Utrecht, Wilhelmina Children's hospital
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Limburg
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Maastricht, Limburg, Netherlands, 6202 AZ
- Academic Hospital Maastricht
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- all subtypes of JIA according to ILAR criteria
- ages 4 to 9 (before the scheduled booster, normally administered at age 9 in the Netherlands)
- 5 healthy adults (aged 18 to 65y)
Exclusion Criteria:
- use of Infliximab (Remicade, anti-Tumor Necrosis Factor (TNF) alpha therapy).
- primary immunodeficiency
- fever less than 48 hour prior to vaccination (vaccination will be postponed for 1 month)
- evidence of viral or bacterial infection less than 48hours prior to vaccination (vaccination will be postponed for 1 month)
- methylprednisolone pulse therapy less than 1 month prior to vaccination (vaccination will be postponed for 1 month)
- transfusion of blood or blood products (e.g. intravenous immunoglobulins (IVIG)) in the 3 months prior to vaccination (vaccination will be postponed for 3 months)
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: 1
Measles, mumps, rubella booster vaccination within 3 months after randomisation
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Dosage: 1 dose MMR vaccine, containing 5000 p.f.u.
(plaque forming unit) life attenuated mumps virus (Jeryl-Lynn-strain), 1000 p.f.u.
life attenuated measles virus (Moraten-strain) and 1000 p.f.u.
life attenuated rubella virus (Wistar RA 27/3-strain) + 0.5 ml solution fluid Dosage form: subcutaneously frequency: once
Other Names:
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No Intervention: 2
Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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JIA disease activity, defined by the core set criteria for JIA and number of flares
Time Frame: baseline and after 3, 6,9,12 months
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baseline and after 3, 6,9,12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Immunological reaction to MMR vaccination and regulatory mechanisms induced by MMR, measured by number and function of MMR-specific T cells and cytokine profiles
Time Frame: baseline, 3 and 12 months
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immunogenicity measuring antibody titers and T cell profileration to rubella virus
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baseline, 3 and 12 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nico M. Wulffraat, MD;PhD, UMC Utrecht
Publications and helpful links
General Publications
- Heijstek MW, Pileggi GC, Zonneveld-Huijssoon E, Armbrust W, Hoppenreijs EP, Uiterwaal CS, Kuis W, Wulffraat NM. Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis. Ann Rheum Dis. 2007 Oct;66(10):1384-7. doi: 10.1136/ard.2006.063586. Epub 2007 Feb 6.
- Zonneveld-Huijssoon E, Ronaghy A, Van Rossum MA, Rijkers GT, van der Klis FR, Sanders EA, Vermeer-De Bondt PE, Hoes AW, van der Net JJ, Engels C, Kuis W, Prakken BJ, Van Tol MJ, Wulffraat NM. Safety and efficacy of meningococcal c vaccination in juvenile idiopathic arthritis. Arthritis Rheum. 2007 Feb;56(2):639-46. doi: 10.1002/art.22399.
- Heijstek MW, Kamphuis S, Armbrust W, Swart J, Gorter S, de Vries LD, Smits GP, van Gageldonk PG, Berbers GA, Wulffraat NM. Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial. JAMA. 2013 Jun 19;309(23):2449-56. doi: 10.1001/jama.2013.6768.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Morbillivirus Infections
- Paramyxoviridae Infections
- Mononegavirales Infections
- Togaviridae Infections
- Rubivirus Infections
- Arthritis
- Measles
- Arthritis, Juvenile
- Rubella
Other Study ID Numbers
- VAART
- ISRCTN12271664
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