Rheumatoid Arthritis Induction Trial (RAITMAT)

类风湿性关节炎诱导试验 (RAITMAT)

• 批准号: 7293416
• 负责人: LARRY W MORELAND
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7293416
• 关键词: Accounting; Adrenal Cortex Hormones; Affect; Aftercare; Age; Anti-Tumor Necrosis Factor Therapy; Anti-citrullinated peptide antibody; Arthritis; Arts; Autoantibodies; Biological Markers; Blinded; C-reactive protein; Clinical; Clinical Trials; Combined Modality Therapy; Data; Data Collection; Development; Disease; Disease remission; Flare; Funding; Genetic; Genomics; Grant; Holidays; Infection; Informed Consent; Intervention; Joints; Label; Lead; Manuals; Messenger RNA; Methotrexate; Molecular Profiling; Neoadjuvant Therapy; Numbers; Onset of illness; Operative Surgical Procedures; Oral; Outcome; Participant; Patient Selection; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Placebos; Prednisone; Procedures; Process; Proteomics; Protocols documentation; Quality Control; Race; Randomized; Relative (related person); Research; Research Personnel; Rheumatoid Arthritis; Score; Secure; Serious Adverse Event; Serological; Signs and Symptoms; Smoking; TNF gene; Technology; Teleconferences; Time; Toxic effect; Treatment Protocols; Treatment outcome; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Unemployment; Week; Withdrawal; Work; Writing; arthritis therapy; cost effective; cytokine; day; design; disability; experience; human TNF protein; instrument; novel; novel therapeutics; placebo controlled study; prevent; prototype; response; sex

DESCRIPTION (provided by applicant): Recent data support the possibility of inducing a remission in a large number of RA patients receiving combination therapy; this data supports the need and the design of this "Rheumatoid Arthritis Induction Trial with methotrexate and anti-TNF therapy (RAITMAT) study. Our hypothesis is that patients with early rheumatoid arthritis (RA) when treated with a combination of methotrexate, anti-tumor necrosis factor (anti-TNF) agent and oral corticosteroids will be able to induce a remission in 50% of subjects at 12 months, and that 50% there subjects will remain in remission at least 12 months after discontinuing the anti-TNF agent in a blinded manner. This important study will establish the most cost effective ways to manage early RA patients, while avoiding intermediate-term joint damage, disability and unemployment. The anti-TNF free holidays may also minimize serious adverse events, such as infections. In addition, we will propose state of the art mechanistic studies that will provide the framework for studying the disease and its variability among subjects, as well as potential biomarkers that might be useful to predict response (or lack of response) to this induction therapy. A steering committee of clinical trialists, biostatisticians, and basic researchers has been formed to design the RAITMAT trial. A clinical trials planning grant is needed for the following specific aims: 1.) Conduct meetings and teleconferences of the steering committee to write the grants needed for funding of the RAITMAT trial; 2.) Develop study materials such as manual of operations & procedures, quality control procedures, informed consent prototype, and data collection instruments; 3.) Secure study medications from pharmaceutical/biotech companies; and 4.) Finalize mechanistic studies to be performed. This proposal brings together an experienced group of investigators involved with RA research. We will prospectively analyze the molecular signatures of responses to treatment with combinations of RA therapies that will induce remission. The results of these studies will provide novel information on best treatment approaches in patients with early aggressive RA. An important objective of the proposed trial will be to identify proteomic and/or genomic biomarkers to guide patient selection and therapy. Technologies to be evaluated include autoantibody, cytokine, mRNA, and other biomarker profiling technologies. This project seeks to gather intellectual expertise to develop mechanism and protocol by which to evaluate mechanistic studies and potential biomarkers for evidence of the short term benefits of powerful treatment regimens used in the course of early aggressive intervention of rheumatoid arthritis. This will lead to the development of the proposed Rheumatoid Arthritis Induction Trial with MTX and Anti-TNF Therapy (RAITMAT).

描述（由申请人提供）：最近的数据支持在大量接受联合治疗的RA患者中诱导缓解的可能性;该数据支持本“甲氨蝶呤和抗TNF治疗的风湿性关节炎诱导试验（RAITMAT）研究”的需求和设计。我们的假设是，早期类风湿性关节炎（RA）患者接受甲氨蝶呤、抗肿瘤坏死因子（抗TNF）药物和口服皮质类固醇联合治疗时，12个月时50%的受试者能够诱导缓解，并且50%的受试者在盲态下停用抗TNF药物后至少12个月仍能保持缓解。这项重要的研究将建立最具成本效益的方法来管理早期RA患者，同时避免中期关节损伤，残疾和失业。抗TNF免费假期也可以最大限度地减少严重的不良事件，如感染。此外，我们将提出最先进的机制研究，这些研究将为研究疾病及其受试者之间的变异性提供框架，以及可能有助于预测对这种诱导治疗的应答（或无应答）的潜在生物标志物。一个由临床试验者、生物统计学家和基础研究人员组成的指导委员会已经成立，以设计RAITMAT试验。临床试验计划补助金需要用于以下具体目标：1。召开指导委员会的会议和电话会议，编写资助RAITMAT试验所需的赠款; 2.）开发研究材料，如操作和程序手册、质量控制程序、知情同意原型和数据收集工具; 3.）从制药/生物技术公司获得研究药物;以及4.）最后确定要进行的机制研究。该提案汇集了一批参与RA研究的经验丰富的研究人员。我们将前瞻性分析RA联合治疗缓解的分子特征。这些研究的结果将为早期侵袭性RA患者的最佳治疗方法提供新的信息。拟议试验的一个重要目标是确定蛋白质组学和/或基因组生物标志物，以指导患者选择和治疗。待评估的技术包括自身抗体、细胞因子、mRNA和其他生物标志物分析技术。该项目旨在收集知识专长，以开发机制和方案，通过这些机制和方案来评估机制研究和潜在的生物标志物，以证明在类风湿关节炎的早期积极干预过程中使用的强大治疗方案的短期益处。这将导致拟定的MTX和抗TNF治疗的风湿性关节炎诱导试验（RAITMAT）的开发。