Trainet: Diabetes Type 1 Prevention

描述(申请人提供)：长期目标：寻找能够延缓、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疫苗治疗新发1型糖尿病 研究设计：在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。在小鼠和非人类灵长类动物上进行的临床前研究发现，这种疗法没有毒性，并建议了一种可能对患有T1D的人类受试者有效的剂量方案。一项正在进行的第1阶段研究证实了这种治疗的安全性，并建议在确诊后3个月仍有C肽存在的1型糖尿病患者中具有潜在的疗效。目前的试验将测试2剂，1毫克和3毫克，在新发病的患者群体中每周12剂。它将使用既定的措施来确定对C肽、糖化血红蛋白、总胰岛素使用量和其他安全参数的影响。将进行机制研究，以观察对胰岛素和其他自身抗体、T细胞和其他免疫效应的影响，以更好地了解影响的潜在机制。 2)更新TrialNet中心 研究设计：芭芭拉·戴维斯中心在确定T1D和其他自身免疫性疾病的风险人群以及为TrialNet自然史研究和其他TrialNet研究招募患者方面一直处于领先地位。BDC TrialNet中心帮助开发了第一批方案中的两个，TN02(MMF和DZB用于新发的T1D)和TN06(预防[NIP]糖尿病的营养干预)。我们的更新建议概述了我们过去的努力、目前的做法和未来目标，不仅是为了保持我们目前的生产率水平，而且是为了在下一个供资周期提高生产率。 公共卫生相关性：这项研究的目的是研究预防糖尿病和/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。

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.