CLINICAL TRAILS IN PEDIATRIC RHEUMATOLOGY

描述（摘自申请人摘要）：本申请专注于 两项前瞻性、多中心试验的表现， 幼年类风湿性关节炎（JRA）。此外，这项职业发展补助金 旨在提高许多儿科风湿病中心的能力， 北美进行试验，以确定疗效和安全性 目前正在使用但未经测试的药物，也是新开发的用于JRA儿童的药物 通过提高主要研究者（PI）的能力， 指导和协调儿科流变学的工作 协作研究小组（PRCSG），PI担任主席。PRCSG是 超过45个学术儿科风湿病中心的联盟， 在患有JRA的儿童中进行了30多项试验。 试验1：骨质减少是JRA的一种显著且常见的并发症。这 研究方案包括一项前瞻性、随机、多中心、 安慰剂对照试验（RCT），以确定每日口服钙的疗效 补充（1000毫克/天的碳酸钙）两年，以增加 与安慰剂相比，全身骨密度（TB BMD）降低10%（1.5 SD） 治疗此外，治疗效果的持久性将是 在RCT后1.5年确定。这将是第一个纵向 对JRA和对照组的骨矿化研究将证明， 骨矿化的自然史。 试验2：这项研究计划还包括一项前瞻性、随机、 积极控制，开放的临床试验，以确定疗效 诱导儿童长期无药缓解的联合药物治疗 严重系统性JRA（sJRA）。患者将在疾病早期入组 当然，资格标准将选择那些有115%的风险， 发展成严重的侵蚀性多关节炎一种治疗方案包括 静脉注射甲泼尼龙，连续3天，静脉注射 环磷酰胺第三天，和高达20毫克/平方米/周的甲氨蝶呤。的 第二脉冲治疗方案与第一脉冲治疗方案相同，除了 给予环磷酰胺。这些方案最多可在一个疗程内给药5个周期。 9-月期间。两组患者也可能接受背景药物治疗 包括1种非甾体抗炎药和最多0.5 mg/kg/d的口服 强的松这些治疗的短期和中期（0-18个月）安全性 将比较方案。 长期目标：1。评估当前和新兴药物的疗效和安全性 药物和生物治疗作为JRA钙的连续治疗 骨质疏松患者。2.确定长期疗效和安全性 sJRA的治疗方案。

DESCRIPTION (Taken from the applicant's abstract): This application is focused on the performance of two prospective, multicentered trials in children with juvenile rheumatoid arthritis (JRA). In addition, this career development grant is intended to enhance the ability of many pediatric rheumatology centers in North America to perform trials to determine the efficacy and safety of currently used but untested and also newly developed drugs in children with JRA by increasing the ability of the principal investigator (PI) to focus on the direction and coordination of the efforts of the Pediatric Rheumatology Collaborative Study Group (PRCSG) of which the PI is the chairman. The PRCSG is a consortium of over 45 academic pediatric rheumatology centers that have performed over 30 trials in children with JRA. Trial 1: Osteopenia is a significant and frequent complication of JRA. This research proposal includes a prospective, randomized, multicenter, placebo-controlled trial (RCT) to determine the efficacy of daily oral calcium supplementation (1000 mg/day of calcium carbonate) for two years to increase total body bone mineral density (TB BMD) by 10% (1.5 SD) compared to placebo treatment. In addition, the persistence of the treatment effect will be determined for 1.5 years after the RCT. This will be the first longitudinal study of bone mineralization in JRA and the control group will demonstrate the natural history of bone mineralization. Trial 2: This research proposal also includes a prospective, randomized, actively controlled, open clinical trial to determine the efficacy of combination drug therapy to induce prolonged drug-free remission in children with severe systemic JRA (sJRA). Patients will be enrolled early in the disease course but eligibility criteria will select those with a 115% risk of developing severe, erosive polyarthritis. One therapy regimen is composed of intravenous methylprednisolone for 3 consecutive days, intravenous cyclophosphamide on the third day, and up to 20 mg/M2/wk of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to 5 cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including 1 non-steroidal anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednisone. The short and intermediate (0-18 months) safety of these treatment regimens will be compared. Long-term goals: 1. Assess the efficacy and safety of current and emerging pharmacologic and biologic treatments as adjunctive therapy to calcium in JRA patients with osteopenia. 2. Determine the long-term efficacy and safety of these treatment regimens in sJRA.