Type 1 Diabetes TrialNet: Toronto Clinical Centre

1 型糖尿病 TrialNet：多伦多临床中心

• 批准号: 8287984
• 负责人: DIANE K WHERRETT
• 金额: $ 43.81万
• 依托单位: HOSPITAL FOR SICK CHLDRN (TORONTO)
• 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 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287984
• 关键词: Affect; American; Area; Autoimmunity; Beta Cell; C-Peptide; Cells; Child; Clinical; Clinical Immunology; Clinical Trials; Complications of Diabetes Mellitus; Development; Diabetes Mellitus; Disease; Double-Blind Method; Future; Glucose tolerance test; Glutamate Decarboxylase; Health; Hospitals; Hour; Human; Hypoglycemia; Immune; Insulin; Insulin-Dependent Diabetes Mellitus; Kidney Diseases; Leadership; Mediating; Methods; Monoclonal Antibody CD20; Natural History; Patients; Pharmaceutical Preparations; Placebo Control; Recombinants; Research Personnel; Resources; Retinal Diseases; Roche brand of rituximab; Safety; Severities; Study Subject; Testing; Universities; aluminum sulfate; exenatide; improved; insulin secretion; mimetics; prevent; primary outcome; public health relevance; regenerative; rituximab; success

DESCRIPTION (provided by applicant): The first objective of this application is describe the strengths and successes of the TrialNet Clinical Center at the Hospital for Sick Children/University of Toronto. The Toronto Clinical Center has shown a high level of recruitment for the TrialNet Natural History of the Development of Type 1 Diabetes Study through its highly capable investigators, Drs. Diane Wherrett and Jeffrey Mahon, providing expertise in diabetes, clinical trials and immunology of type 1 diabetes, its excellent coordinators, institutional support and resources, a productive Canadian affiliate network and extensive local partnerships in the Toronto area. Recruitment to this study ranks 4th of the 14 North American TrialNet Clinical Centers. This center has provided leadership in TrialNet studies: Dr. Mahon, chair of the Natural History Study of the Development of Type 1 Diabetes Study and Dr. Wherrett, chair of the Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects Study. It has contributed actively to all of TrialNet's studies to preserve insulin secretion in recent onset diabetes. The second objective is to determine the efficacy and safety of the incretin mimetic exenatide (Byetta(), alone and in combination with the anti-CD20 monoclonal antibody rituximab (Rituxan(), in patients with newly recognized immune-mediated Type 1 Diabetes. The proposal's primary objective will be to test the hypothesis that the combination of exenatide and rituxamab more effectively preserves endogenous insulin secretion compared to either drug alone. The primary outcome will be the area under the stimulated C-peptide curve (AUC) during a 2 hour mixed meal glucose tolerance test one year after study entry. The study will be placebo controlled and double blinded. The rationale for this proposed study combines the immunomodulatory effect of rituximab to reduce beta cell autoimmunity with the beta cell regenerative potential of exenatide to improve insulin secretion. Preserved endogenous insulin secretion has been found to be associated with reduced of rates of the diabetes complications of hypoglycemia, nephropathy and retinopathy. PUBLIC HEALTH RELEVANCE: Finding methods to preserve insulin secretion in type 1 diabetes are crucial in preventing the disease and in reducing the severity in those affected. The combination of rituximab and exenatide has the potential to both reduce the loss of insulin-producing cells and to promote their development. Success of this therapy could result in the improvement of long term health for those with type 1 diabetes.

描述（由申请人提供）：本申请的第一个目标是描述多伦多大学儿童医院 TrialNet 临床中心的优势和成功。多伦多临床中心通过其高素质的研究人员 Drs. TrialNet 的 1 型糖尿病发展自然史研究进行了高水平的招募。 Diane Wherrett 和 Jeffrey Mahon 提供糖尿病、1 型糖尿病临床试验和免疫学方面的专业知识、优秀的协调员、机构支持和资源、富有成效的加拿大附属网络以及多伦多地区广泛的当地合作伙伴关系。这项研究的招募人数在 14 个北美 TrialNet 临床中心中排名第四。该中心在 TrialNet 研究中发挥了领导作用：Mahon 博士是 1 型糖尿病发展自然史研究的主席，Wherrett 博士是明矾中配制的重组人谷氨酸脱羧酶 (rhGAD65) (GAD-alum) 对新发受试者 1 型糖尿病进展的影响研究的主席。它为 TrialNet 的所有研究做出了积极贡献，以在新发糖尿病中保持胰岛素分泌。第二个目标是确定肠促胰岛素模拟物艾塞那肽（Byetta（））单独使用以及与抗 CD20 单克隆抗体利妥昔单抗（Rituxan（））联合使用，对新发现的免疫介导的 1 型糖尿病患者的疗效和安全性。该提案的主要目的是检验艾塞那肽和利妥昔单抗联合使用更有效地保护糖尿病患者的假设。 与单独使用任一药物相比，内源性胰岛素分泌。主要结果将是研究开始一年后 2 小时混合餐葡萄糖耐量测试中刺激 C 肽曲线下的面积 (AUC)。该研究将采用安慰剂对照和双盲方式。这项拟议研究的基本原理是将利妥昔单抗减少 β 细胞自身免疫的免疫调节作用与 β 细胞再生潜力结合起来。 艾塞那肽可改善胰岛素分泌。已发现保留的内源性胰岛素分泌与低血糖、肾病和视网膜病等糖尿病并发症的发生率降低有关。 公共卫生相关性：寻找保持 1 型糖尿病胰岛素分泌的方法对于预防该疾病和减轻受影响者的严重程度至关重要。利妥昔单抗和艾塞那肽的组合有可能减少胰岛素生成细胞的损失并促进其发育。这种疗法的成功可能会改善 1 型糖尿病患者的长期健康状况。