Trainet: Diabetes Type 1 Prevention

培训班：1 型糖尿病预防

• 批准号: 8284422
• 负责人: PETER A GOTTLIEB
• 金额: $ 39.78万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284422
• 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. PUBLIC HEALTH RELEVANCE: The purpose of this research is to investigate methods to prevent diabetes and/or to prolong insulin production in people who have been recently diagnosed with type 1 diabetes.

描述（由申请人提供）：长期目标：找到可以延迟，预防或扭转1型糖尿病（T1D）的干预疗法。 具体目的： 1）BHT-3021近期1型糖尿病受试者的促硫素DNA疫苗治疗 研究设计：动物的初步数据表明，使用类似的原硫磺蛋白DNA疫苗可以逆转高血糖小鼠的糖尿病。在小鼠和非人类灵长类动物的临床前研究发现对这种疗法没有毒性，并提出了一种剂量方案，该方案可能对具有T1D的人类受试者有效。一项正在进行的第一阶段研究证实了这种治疗方法的安全性，并提出了诊断> 3个月> 3个月的1型糖尿病受试者的潜在功效，但仍存在C肽。当前的试验将测试2剂，1和3 mg，每周在新的发病患者人群中为12剂提供12剂。它将采取已建立的措施来确定对C肽，HBA1C，总胰岛素使用和其他安全参数的影响。将进行对胰岛素和其他自身抗体，T细胞和其他免疫作用的影响的机理研究，以更好地了解潜在的效果机理。 2）续签试验中心 研究设计：芭芭拉·戴维斯中心（Barbara Davis Center）一直处于定义有T1D和其他自身免疫性疾病风险的人群以及招募患者进行试验网络自然史研究以及其他试验网研究的最前沿。 BDC试验中心有助于开发两个第一个方案TN02（新发作T1D中的MMF和DZB）和TN06（营养干预措施，以防止[NIP]糖尿病）。我们的更新建议概述了我们过去的努力，当前的方法和未来的目标，不仅要保持我们当前的生产力水平，而且还提高了下一个融资周期的生产率。 公共卫生相关性：这项研究的目的是调查预防糖尿病和/或延长最近被诊断为1型糖尿病的人的胰岛素产生的方法。