Trainet: Diabetes Type 1 Prevention

培训班：1 型糖尿病预防

• 批准号: 8490602
• 负责人: PETER A GOTTLIEB
• 金额: $ 54.8万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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/8490602
• 关键词: Animals; Autoantibodies; Autoimmune Diseases; C-Peptide; DNA Vaccines; Data; Development; Diabetes Mellitus; Diagnosis; Dietary Intervention; Dose; Double-Blind Method; Funding; Future; Glycosylated hemoglobin A; Goals; Hyperglycemic Mice; Immune; Insulin; Insulin-Dependent Diabetes Mellitus; Measures; Methods; Mus; Natural History; Patients; Placebo Control; Populations at Risk; Prevention; Principal Investigator; Production; Productivity; Proinsulin; Protocols documentation; Randomized; Recruitment Activity; Research; Research Design; Safety; Scheme; T-Lymphocyte; Testing; Therapeutic Intervention; Toxic effect; human subject; insulin dependent diabetes mellitus onset; nonhuman primate; patient population; phase 1 study; phase 2 study; preclinical study; prevent; programs; public health relevance

DESCRIPTION (provided by applicant): Long-term objective: To find intervention therapies that can delay, prevent or reverse the development of type 1 diabetes (T1D). Specific Aims: 1) BHT-3021 Proinsulin DNA vaccine treatment of recent onset type 1 diabetes subjects Research Design: Preliminary data in animals has shown that using a similar proinsulin DNA vaccine can reverse diabetes in hyperglycemic mice. Pre-clinical studies in mice and non-human primates have found no toxicity for this therapy and have suggested a dosing scheme which could be effective in human subjects with T1D. An ongoing phase 1 study has confirmed the safety of this treatment and has suggested potential efficacy in type 1 diabetes subjects >3 months from diagnosis who still have C-peptide present. The current trial will test 2 doses, 1 and 3 mg, given weekly for 12 doses in a new onset patient population. It will use established measures to determine the effect on C-peptide, HbA1c, total insulin use and other safety parameters. Mechanistic studies to look at effects on insulin and other autoantibodies, T cells and other immune effects will be performed to better understand the potential mechanism of effect. 2) Renewal of TrialNet Center Research Design: The Barbara Davis Center has been at the forefront of defining populations at risk for T1D and other autoimmune diseases and in recruiting patients for the TrialNet Natural History study as well as other TrialNet studies. The BDC TrialNet Center has helped to develop two of the first protocols, TN02 (MMF and DZB in new onset T1D), and TN06 (Nutritional Intervention to Prevent [NIP] Diabetes). Our proposal for renewal outlines our past efforts, current approaches and future goals to not only maintain our current level of productivity, but to increase productivity over the next funding cycle.

描述（由申请人提供）： 长期目标：寻找可以延缓、预防或逆转 1 型糖尿病 (T1D) 发展的干预疗法。 具体目标： 1) BHT-3021胰岛素原DNA疫苗治疗近期发病的1型糖尿病受试者 研究设计：动物身上的初步数据表明，使用类似的胰岛素原 DNA 疫苗可以逆转高血糖小鼠的糖尿病。对小鼠和非人类灵长类动物的临床前研究发现这种疗法没有毒性，并提出了一种对患有 T1D 的人类受试者有效的剂量方案。一项正在进行的 1 期研究证实了这种治疗的安全性，并表明对诊断后 3 个月内仍存在 C 肽的 1 型糖尿病受试者具有潜在疗效。目前的试验将测试 2 种剂量，即 1 毫克和 3 毫克，每周在新发病患者群体中注射 12 剂。它将使用既定的措施来确定对 C 肽、HbA1c、总胰岛素使用量和其他安全参数的影响。将进行机制研究，以了解对胰岛素和其他自身抗体、T 细胞和其他免疫效应的影响，以更好地了解潜在的影响机制。 2) TrialNet中心更新 研究设计：Barbara Davis 中心在确定 T1D 和其他自身免疫性疾病风险人群以及招募患者参加 TrialNet 自然历史研究以及其他 TrialNet 研究方面一直处于领先地位。 BDC TrialNet 中心帮助开发了两个首批方案：TN02（新发 T1D 中的 MMF 和 DZB）和 TN06（预防 [NIP] 糖尿病的营养干预）。我们的更新提案概述了我们过去的努力、当前的方法和未来的目标，不仅要维持当前的生产力水平，还要提高下一个融资周期的生产力。