Clinical trial NCT00731965: Safety and Efficacy of Measles, Mumps, Rubella Vaccination in Juvenile Idiopathic Arthritis
Official title: Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Juvenile Rheumatoid
Keywords: Arthritis, Juvenile Rheumatoid
Measles-Mumps-Rubella Vaccine
Serology
Lymphocytes
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
name: Amsterdam UMC, location VUmc
name: Maastricht University Medical Center
name: Erasmus Medical Center
First posted: 2008-08-11
Enrollment: 140
Sex: ALL
Minimum age (years): 4
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility 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)

Primary outcomes:
measure: JIA disease activity, defined by the core set criteria for JIA and number of flares
timeFrame: baseline and after 3, 6,9,12 months
Secondary outcomes:
measure: Immunological reaction to MMR vaccination and regulatory mechanisms induced by MMR, measured by number and function of MMR-specific T cells and cytokine profiles
timeFrame: baseline, 3 and 12 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Academic hospital Maastricht
state: Limburg
city: Amsterdam
country: Netherlands
facility: VU University Medical Center Amsterdam
city: Groningen
country: Netherlands
facility: University Medical Center Groningen, Beatrix Children's Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Rotterdam; sophia Children's Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht, Wilhelmina Children's Hospital
Study officials:
affiliation: UMC Utrecht
name: Nico M. Wulffraat, MD;PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1136/ard.2006.063586. Epub 2007 Feb 6.
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. doi: 10.1002/art.22399.
citation: 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.