Type 1 Diabetes TrialNet at Indiana University Clinical Center

印第安纳大学临床中心 1 型糖尿病 TrialNet

• 批准号: 7938580
• 负责人: LINDA A DIMEGLIO
• 金额: $ 82.33万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938580
• 关键词: Age; Animal Model; Autoantibodies; Autoimmune Diabetes; Autoimmune Diseases; B-Cell Lymphomas; Beta Cell; Cell physiology; Chronic; Clinical; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Eligibility Determination; Functional disorder; Human; Hyperglycemia; Immune; Immunologics; Indiana; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; International; Intervention; Intervention Studies; Investigation; Islets of Langerhans; Mediating; Modality; Natural History; Organ Transplantation; Outcome; Patients; Pharmaceutical Preparations; Physicians; Prevention; Principal Investigator; Protocols documentation; Qualifying; Randomized; Recruitment Activity; Relative (related person); Research; Research Design; Rheumatoid Arthritis; Risk; Safety; San Francisco; Site; Staging; Structure of beta Cell of islet; Symptoms; T-Lymphocyte; Treatment Efficacy; Universities; clinical research site; islet; meetings; novel; proband; public health relevance; rituximab

DESCRIPTION (provided by applicant): Type 1 diabetes arises in genetically predisposed individuals as a consequence of the immune-mediated destruction of the pancreatic islet insulin secreting beta cells. The onset of clinical symptoms of diabetes represents a relative endpoint in the chronic progressive decline of beta cell function, and occurs when a preponderance of beta cell mass is lost. The Diabetes Prevention Trial -Type 1 (DPT-1) and Type 1 Diabetes TrialNet have shown: 1) that multi-center cooperative research in type 1 diabetes can be efficiently coordinated on a national and international level and 2) that type 1 diabetes can be predicted with a high degree of accuracy in relatives of patients with type 1 diabetes by the presence of autoantibodies and evidence of pancreatic beta-cell dysfunction. These studies have enabled identification of a large number of patients at the very early stages of their disease prior to the onset of hyperglycemia. Evidence, both in animal models of type-1 diabetes and in human trials, has shown that it is possible to alter the course of beta cell destruction utilizing numerous interventions. Increasingly, novel immunologic agents characterized in investigations of other autoimmune disorders and in the field of organ transplantation have been proposed for the treatment of autoimmune diabetes. One such agent, the anti-CD20 drug rituximab (RituxanR, Genentech, South San Francisco and Biogen) originally developed for treatment of B-cell lymphoma, is now approved for treatment of rheumatoid arthritis, another classically T-cell mediated disease. Results of the TrialNet Rituximab new-onset intervention study, designed by the Co-PI for this study proposal Dr. Mark Pescovitz, has now provided evidence for safety and efficacy of this treatment modality in type 1 diabetes. We propose to extend and expand our participation in Type 1 Diabetes TrialNet as a Clinical Center. As the Clinical Center that proposed the use of rituximab in a new-onset intervention trail and the leader in subject recruitment for that study, IU is uniquely qualified to conduct a prevention study utilizing this agent. PUBLIC HEALTH RELEVANCE: This application is in accordance with the RFA-DK-08-011 solicitation to invite sites to apply to become TrialNet Clinical Centers. Centers will carry out the TrialNet Natural History Study and prevention and new-onset intervention studies while overseeing a network of Affiliate Centers and additional clinical sites that will recruit and follow individuals with T1D and those at risk for development of the disease.

描述(申请人提供)：1型糖尿病发生在遗传易感的个人，作为免疫介导性破坏胰岛胰岛素分泌的β细胞的结果。糖尿病临床症状的出现代表了胰岛β细胞功能慢性进行性下降的相对终点，当大部分胰岛细胞团块丧失时就会发生。1型糖尿病预防试验(DPT-1)和1型糖尿病试验网络表明：1)多中心的1型糖尿病合作研究可以在国家和国际层面上有效地协调；2)通过自身抗体的存在和胰腺β细胞功能障碍的证据，1型糖尿病患者的亲属可以高度准确地预测1型糖尿病。这些研究使大量患者能够在高血糖发作之前确定其疾病的非常早期阶段。 无论是在1型糖尿病的动物模型中，还是在人体试验中，证据都表明，利用多种干预措施，改变β细胞的破坏过程是可能的。以研究其他自身免疫性疾病和器官移植为特征的新型免疫学药物越来越多地被提出用于治疗自身免疫性糖尿病。其中一种药物是抗CD20药物利妥昔单抗(RituxanR，Genentech，South San Francisco and Biogen)，最初是为治疗B细胞淋巴瘤而开发的，现在被批准用于治疗类风湿性关节炎，这是另一种经典的T细胞介导的疾病。由Co-PI为这项研究建议Mark Pescovitz博士设计的TrialNet Rituximab新发病干预研究的结果现在已经为这种治疗方式在1型糖尿病中的安全性和有效性提供了证据。 我们建议扩大和扩大我们作为临床中心参与的1型糖尿病试验网络。作为建议在新的干预试验中使用利妥昔单抗的临床中心和该研究受试者招募的领导者，印第安纳大学是唯一有资格利用这种药物进行预防研究的机构。 公共卫生相关性：本申请是根据RFA-DK-08-011征集邀请网站申请成为TrialNet临床中心。中心将开展TrialNet自然病史研究和预防以及新发干预研究，同时监督附属中心网络和其他临床站点，这些网络将招募和跟踪患有T1D和有疾病发展风险的人。