Type 1 Diabetes TrialNet: Clinical Center at Berrie Center, Columbia University

1 型糖尿病 TrialNet：哥伦比亚大学贝里中心临床中心

• 批准号: 8468695
• 负责人: Raphael A. Clynes
• 金额: $ 23.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468695
• 关键词: Address; Adult; Area; Autoimmunity; B-Lymphocytes; Basic Science; Biological Markers; Biological Preservation; C-Peptide; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Collagen Arthritis; Correlative Study; Cross Presentation; Development; Diabetes Mellitus; Disease; Environment; Evaluation; Fertilization; Fostering; Human; Inbred NOD Mice; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention Studies; Intervention Trial; Lupus; Lupus Nephritis; Natural History; New York City; Outcome; Patients; Phase; Prevention; Randomized; Research; Research Design; Research Subjects; Rheumatoid Arthritis; SYK gene; Scientist; Site; Systemic Lupus Erythematosus; T-Cell Activation; T-Lymphocyte; Therapeutic; Toxic effect; Translational Research; Universities; base; clinical care; design; human SYK protein; human subject; inhibitor/antagonist; insight; interest; member; patient population; pre-clinical; preclinical study; prevent; programs; public health relevance; small molecule; therapeutic target; uptake

DESCRIPTION (provided by applicant): The Berrie Center is uniquely situated to contribute to the design and conduct of T1DM trials as part of TrialNet. The Berrie Center combines multi-disciplinary clinical care for patients with diabetes and clinical and basic research programs in diabetes all in one facility. The close geographic proximity of clinicians, scientists, patients, and clinical research subjects facilitates excellent and seamless collaboration and cross-fertilization and provides a unique and vibrant research environment that fosters translational research. The Berrie Center is the only multi- disciplinary diabetes center in New York City, with a large and growing referral base and a staff and patient population interested in type 1 diabetes research. The Berrie Center has been a very productive and contributing member of the TrialNet group. Although we've been a Major Affiliate rather than a Clinical Center for the past several years, our level of participation in the intervention trials has been at the level of a Clinical Center, randomizing 6-7% of total subjects into the treatment and prevention trials. In addition, we have supervised a productive Affiliate Network of 12 TrialNet affiliate sites. Therapeutic targeting of the SYK protein tyrosine kinase is a promising area of clinical investigation. Pre-clinical studies have established that an orally available small molecule syk inhibitor, R788, can prevent collagen-induced arthritis and prevent/treat NZB/NZW lupus nephritis. Phase II clinical studies in rheumatoid arthritis and ITP have demonstrated encouraging efficacy and manageable toxicities and continued evaluation in these diseases as well as in SLE are on-going. We have demonstrated the ability of R788 to inhibit cross-presentation and T1DM development in NOD mice, providing proof-of principal for this approach in T1DM. As a key component of this TrialNet application, we propose an intervention study to investigate its efficacy in human subjects with new-onset T1DM (onset within 100 days of randomization).

描述（由申请人提供）：作为TrialNet的一部分，Berrie中心处于独特的位置，可以为T1DM试验的设计和实施做出贡献。Berrie中心将糖尿病患者的多学科临床护理和糖尿病的临床和基础研究项目结合在一起。临床医生、科学家、患者和临床研究对象的地理位置接近，促进了卓越和无缝的合作和交叉受精，并提供了一个独特而充满活力的研究环境，促进了转化研究。Berrie中心是纽约市唯一的多学科糖尿病中心，拥有庞大且不断增长的转诊基础以及对1型糖尿病研究感兴趣的工作人员和患者群体。Berrie中心一直是TrialNet小组中一个非常有成效和贡献的成员。虽然在过去的几年中，我们一直是主要附属机构而不是临床中心，但我们在干预试验中的参与水平一直处于临床中心的水平，随机将总受试者的6-7%纳入治疗和预防试验。此外，我们还监督了一个由12个TrialNet附属网站组成的富有成效的附属网络。SYK蛋白酪氨酸激酶的靶向治疗是一个有前途的临床研究领域。临床前研究已经证实口服小分子syk抑制剂R788可以预防胶原诱导的关节炎和预防/治疗NZB/NZW狼疮性肾炎。类风湿性关节炎和ITP的II期临床研究已经证明了令人鼓舞的疗效和可控的毒性，并且正在对这些疾病以及SLE进行持续评估。我们已经证明了R788在NOD小鼠中抑制交叉呈现和T1DM发展的能力，为这种方法在T1DM中的应用提供了主要的证明。作为TrialNet应用程序的关键组成部分，我们提出了一项干预研究，以调查其对新发T1DM（随机分组后100天内发病）的人类受试者的疗效。