Arthritis, Juvenile RheumatoidPhase 4VAARTNCT00731965
Safety and Efficacy of Measles, Mumps, Rubella Vaccination in Juvenile Idiopathic Arthritis
A Phase 4 study testing Measles, Mumps, Rubella vaccination in people with Arthritis, Juvenile Rheumatoid, run by N.M. Wulffraat at 5 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 4 to 9 yearsHealthy volunteers can take part
- Conditions the study is for
- Arthritis, Juvenile Rheumatoid
- What is being tested?
- Measles, Mumps, Rubella vaccination
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 5 sitesNetherlands
- Study dates
- May 2008to May 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 9 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites
VU University Medical Center Amsterdam
Amsterdam, 1007 MB
University Medical Center Groningen, Beatrix Children's Hospital
Groningen, Provincie Groningen, 9700 RB
Academic hospital Maastricht
Maastricht, Limburg, 6202 AZ
Erasmus Medical Center Rotterdam; sophia Children's Hospital
Rotterdam, 3000 CB
University Medical Center Utrecht, Wilhelmina Children's Hospital
Utrecht, Utrecht, 3508 AB
About this study
Official title: Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine
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.
Read more
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
- Being tested
- Measles, Mumps, Rubella vaccination
- Keywords
- Arthritis, Juvenile Rheumatoid, Measles-Mumps-Rubella Vaccine, Serology, Lymphocytes
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measles, Mumps, Rubella vaccinationBiological
Also called RVG 17654, BMR-NVI
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Measles, mumps, rubella booster vaccination within 3 months after randomisation Receives: Biological: Measles, Mumps, Rubella vaccination |
| 2 | No intervention | Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation |
What is being measured
The primary outcome is the main question the study is designed to answer.
JIA disease activity, defined by the core set criteria for JIA and number of flares
Measured: 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
immunogenicity measuring antibody titers and T cell profileration to rubella virus
Measured: baseline, 3 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2008 (estimated)
- Study startMay 2008
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Arthritis, Juvenile RheumatoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- N.M. Wulffraat
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen, Amsterdam UMC, location VUmc, Maastricht University Medical Center, Erasmus Medical Center
- Responsible party
- Sponsor-investigator, N.M. Wulffraat, UMC Utrecht
- Investigators
- Nico M. Wulffraat, MD;PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00731965
- Sponsor's protocol ID
- VAART
- Other IDs
- ISRCTN12271664
- Acronym
- VAART
- Status last verified
- Jul 2014
- First submitted
- 6 Aug 2008
- Last updated
- 30 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17284544Zonneveld-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.
PubMed 17265499Heijstek 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.
PubMed 23780457
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine
- ClinicalTrials.gov ID
- NCT00731965
- Acronym / sponsor ID
- VAART / VAART
- Conditions
- Arthritis, Juvenile Rheumatoid
- Keywords
- Arthritis, Juvenile Rheumatoid, Measles-Mumps-Rubella Vaccine, Serology, Lymphocytes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- N.M. WulffraatUniversity, hospital or other
- Collaborators
- University Medical Center Groningen, Amsterdam UMC, location VUmc, Maastricht University Medical Center, Erasmus Medical Center
- Study start
- May 2008
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 11 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Measles, Mumps, Rubella vaccinationMeasles, mumps, rubella booster vaccination within 3 months after randomisation |
| 2 | No intervention | –Booster vaccination performed by regular health authorities at age 9; at least 1 year after randomisation |
Who may qualify
- Ages
- 4 to 9 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measles, Mumps, Rubella vaccinationAlso: RVG 17654, BMR-NVIDosage: 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 | Biological | 1 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2014.
- Background: PubMed 17284544Heijstek 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.
- Background: PubMed 17265499Zonneveld-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.
- Results publication: PubMed 23780457Heijstek 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nico M. Wulffraat, MD;PhD principal investigator
UMC Utrecht
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Measles, Mumps, Rubella vaccination in people with Arthritis, Juvenile Rheumatoid, run by N.M. Wulffraat at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00731965, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2014.