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

NCT00731965 | Completed Phase 4 DMC

• 2 other identifiers: VAARTISRCTN12271664
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Arthritis, Juvenile Rheumatoid

Keywords

Arthritis, Juvenile Rheumatoid; Measles-Mumps-Rubella Vaccine; Serology; Lymphocytes

Outcome Measures

Primary Outcomes (1)

• JIA disease activity, defined by the core set criteria for JIA and number of flares

  baseline and after 3, 6,9,12 months

Secondary Outcomes (1)

• Immunological reaction to MMR vaccination and regulatory mechanisms induced by MMR, measured by number and function of MMR-specific T cells and cytokine profiles

  baseline, 3 and 12 months

Study Arms (2)

1

EXPERIMENTAL

Measles, mumps, rubella booster vaccination within 3 months after randomisation

Biological: Measles, Mumps, Rubella vaccination

2

NO INTERVENTION

Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation

Interventions

Measles, Mumps, Rubella vaccination BIOLOGICAL

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

Also known as: RVG 17654, BMR-NVI

1

Eligibility Criteria

• Age: 4 Years - 9 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• all subtypes of JIA according to ILAR criteria
• ages 4 to 9 (before the scheduled booster, normally administered at age 9 in the Netherlands)
• healthy adults (aged 18 to 65y)

You may not qualify if:

• 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)

Sponsors & Collaborators

• N.M. Wulffraat: lead
• University Medical Center Groningen: collaborator
• Amsterdam UMC, location VUmc: collaborator
• Maastricht University Medical Center: collaborator
• Erasmus Medical Center: collaborator

Study Sites (5)

Academic hospital Maastricht

Maastricht, Limburg, 6202 AZ, Netherlands

Location

University Medical Center Groningen, Beatrix Children's Hospital

Groningen, Provincie Groningen, 9700 RB, Netherlands

Location

University Medical Center Utrecht, Wilhelmina Children's Hospital

Utrecht, Utrecht, 3508 AB, Netherlands

Location

VU University Medical Center Amsterdam

Amsterdam, 1007 MB, Netherlands

Location

Erasmus Medical Center Rotterdam; sophia Children's Hospital

Rotterdam, 3000 CB, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 17284544 BACKGROUND

• 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.

  PMID: 17265499 BACKGROUND

• 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.

  PMID: 23780457 RESULT

MeSH Terms

Conditions

Arthritis, Juvenile

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Nico M. Wulffraat, MD;PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 11, 2008
• Study Start: May 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: July 30, 2014

Record last verified: 2014-07

Locations

NL (5)