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

Arthritis, Juvenile Rheumatoid Clinical Trial

— VAART  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00731965
• Other study ID #: VAART
• Secondary ID: ISRCTN12271664
• Status: Completed
• Phase: Phase 4
• First received: August 6, 2008
• Last updated: July 29, 2014
• Start date: May 2008
• Est. completion date: May 2012

Study information

• Verified date: July 2014
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Independent Ethics CommitteeNetherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 4 Years to 9 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Arthritis, Juvenile Rheumatoid
• Rubella

Intervention

Biological:
• Measles, Mumps, Rubella vaccination
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

Locations

Country	Name	City	State
Netherlands	VU University Medical Center Amsterdam	Amsterdam
Netherlands	University Medical Center Groningen, Beatrix Children's Hospital	Groningen
Netherlands	Academic hospital Maastricht	Maastricht	Limburg
Netherlands	Erasmus Medical Center Rotterdam; sophia Children's Hospital	Rotterdam
Netherlands	University Medical Center Utrecht, Wilhelmina Children's Hospital	Utrecht

Sponsors (5)

Lead Sponsor	Collaborator
N.M. Wulffraat	Erasmus Medical Center, Maastricht University Medical Center, University Medical Center Groningen, VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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 ar — View Citation

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. Epub 2007 Feb 6. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	JIA disease activity, defined by the core set criteria for JIA and number of flares		baseline and after 3, 6,9,12 months	Yes
Secondary	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	No