Safety and Efficacy of Measles, Mumps, Rubella Vaccination in Juvenile Idiopathic Arthritis

Study Overview
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Brief Summary
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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.

Official Title
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Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine

Conditions
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Arthritis, Juvenile Rheumatoid

Intervention / Treatment
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* Biological: Measles, Mumps, Rubella vaccination


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Measles, mumps, rubella booster vaccination within 3 months after randomisation | Biological: Measles, Mumps, Rubella vaccination<br>* 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<br>* Other names: RVG 17654, BMR-NVI;|
| No Intervention: 2<br>Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| JIA disease activity, defined by the core set criteria for JIA and number of flares |  | baseline and after 3, 6,9,12 months | 

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 | immunogenicity measuring antibody titers and T cell profileration to rubella virus | baseline, 3 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Juvenile Rheumatoid, Measles-Mumps-Rubella Vaccine, Serology, Lymphocytes