Type 1 Diabetes TrialNet: Toronto Clinical Centre

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临床中心TrialNet的优势和成功。多伦多临床中心（Toronto Clinical Center）通过其高水平的研究人员，为1型糖尿病发展自然史研究（TrialNet）提供了高水平的招募。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，其优秀的协调员，机构支持和资源，一个富有成效的加拿大附属网络和在多伦多地区广泛的当地合作伙伴关系。本研究的招募在14个北美试验网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型糖尿病发展自然历史研究的主席，Wherrett博士是明矾中制备的重组人谷氨酸脱羧酶（rhGAD65）对新发病受试者1型糖尿病进展的影响研究的主席。它积极参与了TrialNet的所有研究，以保持近期发病糖尿病的胰岛素分泌。第二个目的是确定拟肠促胰岛素艾塞那肽（Byetta）单独或与抗cd20单克隆抗体利妥昔单抗（Rituxan）联合治疗新发现的免疫介导型1型糖尿病患者的疗效和安全性。该提案的主要目的是验证艾塞那肽和利妥昔单抗联合使用比单独使用任何一种药物更有效地保持内源性胰岛素分泌的假设。主要结果将是研究开始一年后进行2小时混合餐葡萄糖耐量试验时受刺激c肽曲线下的面积。该研究将采用安慰剂对照和双盲法。本研究的基本原理是将利妥昔单抗降低β细胞自身免疫的免疫调节作用与艾塞那肽改善胰岛素分泌的β细胞再生潜力结合起来。已发现保留内源性胰岛素分泌与降低糖尿病并发症低血糖、肾病和视网膜病变的发生率有关。

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.