The primary goal of the current study is to study the safety of and serological response to the MMR booster vaccination in JIA patients. Based on a retrospective analysis we hypothesize that MMR vaccination does not aggravate JIA disease and that…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is safety of vaccination according to:
- disease activity, measured using international validated core set criteria.
During a 12 month follow-up period we will register disease activity
- side-effects as overt measles, mumps or rubella infection due to vaccination.
The second primary outcome is efficacy of the vaccine in eliciting an
serological response, this will be studied according to antibody levels against
measles, mumps and rubella in the blood and presence of MMR neutralizing
antibodies.
Secondary outcome
Secondary endpoints are immunological changes. These are number of Tregs,
capable to suppress proliferation in vitro; presence of anti-inflammatory
cytokine profiles following MMR booster; number of MMR-specific T cells. Tregs
will be isolated and their functionality will be determined using the blood
cells collected during follow-up. the samples of five healthy controls will be
used to construct the necessary immuno assays.
Background summary
The pathogenesis of autoimmune diseases (AID) is largely unknown. It is
generally assumed that AID such as Juvenile Idiopathic Arthritis (JIA) arise in
genetically predisposed patients after environmental triggers like infections.
However, fail-safe mechanisms exist in our immune system. Among others,
regulatory T-cells (Tregs) control the immune response and prevent destructive
autoimmune responses. In order to develop AID after vaccination these
regulatory T-cells and other homeostatic mechanisms must fail. Previous
studies in JIA patients showed no increase in disease activity after
immunization with dead vaccines. A retrospective cohort study showed no
increase in disease activity in JIA patients after the MMR vaccination, a live
attenuated vaccine. A prospective trial was recommended. In addition, it is
unknown whether vaccination is effective in eliciting an serological response,
since the immune response to vaccination may be diminished due to
immunosuppressive therapy for the underlying disease.
Study objective
The primary goal of the current study is to study the safety of and serological
response to the MMR booster vaccination in JIA patients. Based on a
retrospective analysis we hypothesize that MMR vaccination does not aggravate
JIA disease and that patients with active JIA who are under immunosuppressive
medication are still able to mount protective immunity in response to MMR
booster. The secondary objective is to study immune regulatory mechanisms
induced by vaccination. We hypothesize that Tregs are able to prevent relapse
of JIA activity.
Study design
prospective randomized controlled open label vaccination study.
Intervention
One early measles, mumps, rubella (MMR) booster vaccination at the age of 4-9
years.
The MMR vaccine that will be used is already registrated and is currently used
in the National Vaccination Program.
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 randomized in the group with one early MMR booster vaccination
between the age of 4-9 years or in the controlgroup. Patients in the
controlgroup will receive their usual MMR booster vaccine at age 9 according to
the National Vaccination Program. This will be after completion of this study.
Study burden and risks
Burden: 50% of included patients will receive an early MMR booster vaccination
in the hospital, during a regular follow-up visit. In addition, blood will be
obtained for serological and immunological analysis, during routine follow-up
of the patients. Extra visits to the hospital and additional vena punctures are
therefore not required. 2 ml is obtained from all patients for serological
analysis at baseline, after 3 and 12 months. In a subset of patients (n=50),
two times 18 ml instead of 2ml of blood is obtained for immunological analysis
(in total 38ml). in the healthy controls 2 time 25mL blood will be drawn.
Risks: It is possible, however unlikely, that patients will experience an
aggravation of disease.
Benefits: 1) certainty about the protection against measles, mumps and rubella
infections 2)certainty about safety of MMR vaccination and 3) possible
improvement of disease.
Group relatedness: This study can only be done in patients who need this
vaccination (i.e. children) and have an autoimmune disease, such as JIA.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
- all subtypes of juvenile idiopathic arthritis
- ages 4-9 (this is at least 2,5 years after initial MMR and before the scheduled booster, usually given between age 9-10)
- fifteen healthy adults (age 18-65)
Exclusion criteria
- use of Infliximab (anti-TNF alpha therapy).
- primary immunodeficiency
- fever less than 48 hour prior to vaccination (here the moment of vaccination will be postponed for 1 month)
- evidence of viral or bacterial infection less than 48hours prior to vaccination (here the moment of vaccination will be postponed for 1 month)
- methylprednisolon pulse therapy less than 1 month prior to vaccination (in these cases, the moment of vaccination will be postponed for 1 month)
- transfusion of blood or bloodprocudts (e.g.) intravenous immunoglobulines (IVIG) in the 3 months prior to vaccination. (in these cases, the moment of vaccination will be postponed for 3 months);for healthy controls:
-serious adverse events to previous MMR vaccination
-Use of immunosuppressive drugs
-Primary immunodeficiency
-Fever less than 48 hour prior to vaccination (here the moment of vaccination will be postponed for 1 month)
-Evidence of viral or bacterial infection less than 48hours prior to vaccination (here the moment of vaccination will be postponed for 1 month)
-Methylprednisolon pulse therapy less than 1 month prior to vaccination (in these cases, the moment of vaccination will be postponed for 1 month)
-Pregnancy
-Lactation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001861-14-NL |
| Other | ISRTCN 12271664 |
| CCMO | NL17376.000.07 |