DIABETES MELLITUS: PATHOGENESIS AND IMMUNE INTERVENTION

糖尿病：发病机制和免疫干预

• 批准号: 3153499
• 负责人: JAY S SKYLER
• 金额: $ 10.31万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-20 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3153499
• 关键词: autoantibody; autoimmune disorder; cyclosporines; human subject; human therapy evaluation; humoral immunity; immunofluorescence technique; immunosuppressive; immunotherapy; insulin; leukocyte antigen typing; major histocompatibility complex; pancreatic islet function; placebos

The overall objective of this research project is to better clarify the immunopathology associated with Type I insulin dependent diabetes mellitus (IDDM) and to determine if immune intervention alters the course of IDDM. The specific aims include: characterization of a cohort of patients with recent onset IDDM in terms of pancreatic islet beta cell function and immune parameters thought potentially related to the etiopathogenesis of IDDM; definition of the relationship between pancreatic islet beta cell function, various immune parameters, and HLA type; and better definition of the natural history of residual islet beta cell function and various immune parameters during the course of IDDM. In addition, this study will determine the effects of immune intervention with cyclosporine in patients with recent onset IDDM, including: the frequency of complete remission of IDDM, one year after onset, in comparison to a placebo treated control group; the effects of immune intervention with cyclosporine on degree of diabetic control, residual islet beta cell function, and immune parameters thought related to pancreatic islet immunogenicity; the relative efficacy and safety of immune intervention with cyclosporine; the evolution of diabetic microangiopathy, specifically the appearance of diabetic retinopathy and of changes in renal function. The study is a randomized, double-blind, placebo controlled clinical trial evaluating the effects of cyclosporine in patients with Type I Insulin-Dependent Diabetes Mellitus commencing within four weeks of diagnosis. The trial will evaluate up to 100-110 patients, 50-55 patients with each treatment. Patients will be stratified into three groups, prior to randomization, based on the degree of severity of IDDM at the time of initial presentation. Subjects in both treatment categories will be treated with Intensive Insulin Therapy according to the protocol outlined below. Outcome will be judged on the basis of the appearance of complete or partial remissions. Residual endogenous islet beta cell function, as assessed by C-peptide secretion, will be carefully evaluated on a serial basis. Both non-specific and pancreatic islet specific immune parameters will be monitored serially.

该研究项目的总体目标是更好地阐明 与 I 型胰岛素依赖型糖尿病相关的免疫病理学 (IDDM) 并确定免疫干预是否会改变 IDDM 的病程。 具体目标包括： 描述一组患者的特征 最近发生的 IDDM 的胰岛 β 细胞功能和 免疫参数被认为可能与发病机制相关 IDDM；胰岛β细胞之间关系的定义 功能、各种免疫参数和 HLA 类型；以及更好的定义 残余胰岛β细胞功能和各种免疫的自然史 IDDM过程中的参数。 此外，本研究将 确定环孢素免疫干预对患者的效果 最近出现 IDDM，包括： IDDM，发病一年后，与安慰剂治疗对照相比 团体;环孢素免疫干预对程度的影响 糖尿病控制、残余胰岛β细胞功能和免疫参数 认为与胰岛免疫原性有关；相对功效 环孢素免疫干预的安全性和安全性；的演变 糖尿病微血管病变，特别是糖尿病的出现 视网膜病变和肾功能的变化。 该研究是一项随机、双盲、安慰剂对照临床试验 评估环孢素对 I 型患者的作用 胰岛素依赖性糖尿病在 4 周内开始 诊断。 该试验将评估多达100-110名患者、50-55名患者 每次治疗。 患者将被分为三组，之前 根据当时 IDDM 的严重程度进行随机分组 初步介绍。 两个治疗类别的受试者将 根据概述的方案接受强化胰岛素治疗 以下。 结果将根据完整的外观来判断 或部分缓解。 残余内源性胰岛β细胞功能，如 通过 C 肽分泌进行评估，将进行一系列仔细评估 基础。 非特异性和胰岛特异性免疫参数 将被连续监测。