Multicenter Randomized Clinical Trial in Patients With Juvenile Idiopathic Arthritis: Safety and Efficacy of Vaccination With Live Attenuated Measles, Mumps, Rubella Vaccine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 10
- 主要终点
- JIA disease activity, defined by the core set criteria for JIA and number of flares
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 9 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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)
结局指标
主要结局
JIA disease activity, defined by the core set criteria for JIA and number of flares
时间窗: baseline and after 3, 6,9,12 months
次要结局
- 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)
研究者
N.M. Wulffraat
associate professor
UMC Utrecht