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

描述（由申请人提供）：Berrie中心的独特位置有助于设计和开展T1 DM试验，作为TrialNet的一部分。Berrie中心将糖尿病患者的多学科临床护理与糖尿病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非常接近，促进了出色的无缝协作和交叉施肥，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。贝里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人群。Berrie中心一直是TrialNet集团的一个非常富有成效和贡献的成员。虽然我们在过去几年一直是一个主要的附属机构，而不是一个临床中心，但我们参与干预试验的水平一直处于临床中心的水平，将6-7%的受试者随机分配到治疗和预防试验中。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蛋白酪氨酸激酶的治疗靶向是一个有前途的临床研究领域。临床前研究已经确定，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。在类风湿性关节炎和ITP中的II期临床研究已经证明了令人鼓舞的疗效和可管理的毒性，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小鼠中抑制交叉呈递和T1 DM发展的能力，为这种方法在T1 DM中的应用提供了原理性证据。作为该TrialNet应用程序的关键组成部分，我们提出了一项干预研究，以研究其在新发T1 DM（随机化后100天内发病）人类受试者中的疗效。

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).