Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
University Medical Centre Groningen
VU University Medical Center
Maastricht University Medical Center
Erasmus Medical Center
Information provided by (Responsible Party):
N.M. Wulffraat, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00731965
First received: August 6, 2008
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Arthritis, Juvenile Rheumatoid
Biological: Measles, Mumps, Rubella vaccination
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    immunogenicity measuring antibody titers and T cell profileration to rubella virus


Enrollment: 140
Study Start Date: May 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Measles, mumps, rubella booster vaccination within 3 months after randomisation
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
Other Name: RVG 17654, BMR-NVI
No Intervention: 2
Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation

  Eligibility

Ages Eligible for Study:   4 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00731965

Locations
Netherlands
Academic hospital Maastricht
Maastricht, Limburg, Netherlands, 6202 AZ
VU University Medical Center Amsterdam
Amsterdam, Netherlands, 1007 MB
University Medical Center Groningen, Beatrix Children's Hospital
Groningen, Netherlands, 9700 RB
Erasmus Medical Center Rotterdam; sophia Children's Hospital
Rotterdam, Netherlands, 3000 CB
University Medical Center Utrecht, Wilhelmina Children's Hospital
Utrecht, Netherlands, 3508 AB
Sponsors and Collaborators
N.M. Wulffraat
University Medical Centre Groningen
VU University Medical Center
Maastricht University Medical Center
Erasmus Medical Center
Investigators
Principal Investigator: Nico M. Wulffraat, MD;PhD UMC Utrecht
  More Information

Publications:
Responsible Party: N.M. Wulffraat, associate professor, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00731965     History of Changes
Other Study ID Numbers: VAART, ISRCTN12271664
Study First Received: August 6, 2008
Last Updated: July 29, 2014
Health Authority: Netherlands: Independent Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
Arthritis, Juvenile Rheumatoid
Measles-Mumps-Rubella Vaccine
Serology
Lymphocytes

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Rubella
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
RNA Virus Infections
Rheumatic Diseases
Rubivirus Infections
Togaviridae Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014