UCSF TrialNet: A Phase II Trial of hokT3gamma1 (Ala-Ala)

描述（由申请人提供） 本申请的目标是建立TrialNet临床中心， 加州大学旧金山分校弗朗西斯科（UCSF）糖尿病中心， 最终的长期目标是开发治疗方法，以防止型 1例糖尿病（T1DM）。加州大学旧金山分校是唯一定位，作为一个研究 该多中心试验的研究中心，考虑到一个强大的糖尿病项目， 招募受试者的人口基数大，且有良好的往绩记录 临床研究和自身免疫干预治疗T1DM。的临床医生 加州大学旧金山分校糖尿病中心现在为大约3400名患者提供护理，其中100名 1型糖尿病患者每年此外，该中心还 在临床和基础科学方面具有丰富经验的研究人员 研究，并与美国国立卫生研究院资助的儿科和一般临床研究中心。 研究人员有能力从加州大学旧金山分校内部招募受试者 系统，并广泛从整个北方先前存在的转诊网络 加州。人口的多样性表明，受试者将 从不同种族中招募这个应用程序将建立在加州大学旧金山分校？S 曾担任糖尿病预防试验-1（DPT-1）的附属机构。 具体而言，研究目标是：具体目标1：实施和继续 DPT-1协议。这包括建立一个基础设施， 加强对已进入DPT-1的受试者的随访，以及 招募筛选和分期新受试者，随后招募 将中度风险的患者纳入口服胰岛素研究组。 参与通过TrialNet开发的其他试验。具体目标3： 实施一种涉及治疗高风险个体的新方案， 1型糖尿病伴非FcR结合抗CD3单克隆抗体（mAb） （hOKT3g1（Ala-Ala））。一项正在进行的该药物治疗新发T1DM的I/II期试验 已经表明，该药物的给药是安全的，并已表明疗效 在保持胰岛素分泌能力方面。我们这样做的理由 如果在接受化疗的患者中观察到类似的效果， 检测到β细胞功能障碍的最早迹象，然后进展到 糖尿病可以预防。

DESCRIPTION (provided by applicant) The goal of this application is to establish a Clinical Center of TrialNet at the University of California at San Francisco (UCSF) Diabetes Center, with the ultimate long-term objective to develop therapies to prevent the onset of Type 1 diabetes mellitus (T1DM). UCSF is uniquely positioned to serve as a study site for this multicenter trial, given a strong established diabetes program, a large population base for subject recruitment, and an established track record with clinical research and autoimmune interventions for T1DM. Clinicians at the UCSF Diabetes Center now provide care for approximately 3400 patients, with 100 new patients with Type 1 diabetes each year. In addition, the center has investigators with extensive experience in both clinical and basic science research, and with NIH-funded Pediatric and General Clinical Research Centers. The investigators are well positioned to recruit subjects from within the UCSF system, and widely from a preexisting referral net throughout Northern California. The diversity of the population suggests that subjects will be recruited from a variety of ethnicities. This application will build on UCSF?s past role as an Affiliate in the Diabetes Prevention Trial-1 (DPT-1). Specifically, the study goals are: Specific Aim 1: To implement and continue the DPT-1 protocols. This includes creation of an infrastructure that will enhance follow-up of subjects already entered into the DPT-1, as well as recruitment to screen and stage new subjects, with subsequent enrollment of those at intermediate risk into the oral insulin study arm. Specific Aim 2: To participate in other trials developed through TrialNet. Specific Aim 3: To implement a novel protocol involving treatment of individuals at high risk for Type 1 diabetes with a non-FcR binding anti-CD3 monoclonal antibody (mAb) (hOKT3g1(Ala-Ala)). An ongoing Phase I/II trial of this agent in new onset T1DM has shown that administration of the drug is safe, and has suggested efficacy in preserving insulin secretory capacity over time. Our rationale for this application is that if similar effects are seen in patients in whom the earliest signs of beta cell dysfunction are detected, and then progression to diabetes might be prevented.