OXIDATIVE STRESS & CV DENERVATION IN DIABETES: AN INTERVENTIONAL TRIAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。1型糖尿病是一种影响全球数百万人的常见疾病。慢性和致残并发症在这种疾病中很常见，包括一种类型的心血管神经损伤（心血管糖尿病自主神经病变（DAN）），可发生在高达50%的糖尿病患者中。心血管DAN可能通过改变电稳定性和/或损害心脏内的血液流动而引起心律的变化。拟议的研究将利用核医学技术来帮助确定是否可以通过施用三种研究药物来减缓甚至逆转DAN的进展。患有1型糖尿病和轻度至中度DAN的人将有可能参加这项研究。该临床试验是一项双盲、安慰剂对照研究，包括两组；第一组将接受三种研究药物（α -硫辛酸（Alipure）、烟酰胺（Enduramide）和别嘌呤醇（Zyloprim））；第二组将接受匹配的口服安慰剂，为期24个月。参与者将被随机分配到这两组中的一组。主要疗效变量将使用核医学成像技术确定；次要变量将通过利用系统氧化应激和急性相反应物的实验室测量来确定。探索性终点将通过视网膜照片、肾功能测量、心率变异性（HRV）测量和神经病变的临床评估来评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type I diabetes is a common condition affecting millions of individuals worldwide. Chronic and disabling complications are common with this disease, including a type of cardiovascular nerve damage (cardiovascular diabetic autonomic neuropathy (DAN)) that can occur in up to 50% of all people with diabetes. Cardiovascular DAN may cause changes in heart rhythms by altering electrical stability and/or impairing blood flow within the heart. The proposed studies will utilize nuclear medicine techniques to help determine if the progression of DAN can be slowed or even reversed by the administration of three investigational medications. Persons with type 1 diabetes and mild to moderate DAN will potentially be able to enroll in the study. The clinical trial is a double-blind, placebo controlled study consisting of two groups; Group 1 will receive three investigational medications (alpha-lipoic acid (Alipure), nicotinamide (Enduramide), and allopurinol (Zyloprim)); Group 2 will receive matched oral placebos for 24 months. Participants will be assigned randomly to one of these two groups. Primary efficacy variables will be determined using nuclear medicine imaging techniques; secondary variables will be determined by utilizing laboratory measures of systemic oxidative stress and acute phase reactants. Exploratory endpoints will be assessed with retinal photographs, measures of kidney function, measures of heart rate variability (HRV), and clinical assessments of neuropathy.