CLINICAL TRIAL: THE ROLE OF EXENATIDE IN TYPE I DIABETES MELLITUS

临床试验：艾塞那肽在 I 型糖尿病中的作用

• 批准号: 7950635
• 负责人: RUBINA A HEPTULLA
• 金额: $ 1.01万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950635
• 关键词: Adolescent; Adult; Animals; Apoptosis; Beta Cell; Cell Survival; Childhood; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Diagnosis; Dietary Carbohydrates; Dose; Funding; Gastric Emptying; Gastroparesis; Glucagon; Glucose; Grant; Hyperglycemia; Hypoglycemia; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; New Agents; Patients; Pramlintide; Property; Protocols documentation; Randomized; Reporting; Research; Research Personnel; Resources; Role; Source; Testing; United States National Institutes of Health; analog; exenatide; glucagon-like peptide 1; glycemic control; hyperglucagonemia; improved; islet amyloid polypeptide

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 1 diabetes mellitus (T1DM) is currently managed using modulation of dietary carbohydrates and insulin. Parasoxical post-meal hyperglucagonemia is associated with psot-prandial hyperglycemia in T1DM. Glucagon suppressors such as the amylin analog, pramlintide, and the glucagon like peptide-1 (GLP-1) analog, exenatide, are new agents approved for use in adults with diabetes. We have previously demonstrated pramlintide reduces post-prandial hyperglycemia by decreasing glucagon and delaying gastric emptying in adolescents with T1DM. GLP-1 in animal studies has been shown to increase beta cell mass and decrease apoptosis. Only limited information is available on the use of GLP-1 in T1DM. No studies have been reported to determine if pramlintide and exenatide have similar effects on glycemic control in T1DM. The overall aim of this proposal is to develop safe and effective strategies targeting glucagon and improving glycemic control in T1DM. The overall aim of this proposal is to develop safe and effective strategies targeting glucagon and improving glycemic control in pediatric T1DM. The specific aim of Protocol 1 is to establish a glucose-lowering dose of exenatide in T1DM equivalent to that which we have established for pramlintide. To this end 17 subjects with T1DM will be randomized to 4 studies with varying pramlintide doses. Glucagon suppression and delay in gastric emptying will also be assessed. Higher doses of exenatide will result in more pronounced effects on gastric emptying and glucagon suppression as compared to lower doses. SPECIFIC AIMS To establish an effective dose of exenatide, which will normalize post-prandial hyperglycemia without causing hypoglycemia. To determine the effects of exenatide on gastric emptying and glucagon suppression. The long-term objective of this protocol is to develop a safe exenatide dose that can be used in new onset patients with T1DM. The antiapoptic properties of exenatide will be tested to determine if using exenatide early in the diagnosis prolongs beta cell survival and hence prolonging of the honeymoon period of diabetes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 1 型糖尿病 (T1DM) 目前通过调节膳食碳水化合物和胰岛素进行治疗。 餐后副氧高胰高血糖素血症与 T1DM 患者餐后高血糖有关。 胰高血糖素抑制剂，例如胰岛淀粉样多肽类似物普兰林肽和胰高血糖素样肽 1 (GLP-1) 类似物艾塞那肽，是批准用于成人糖尿病患者的新药。 我们之前已经证明，普兰林肽通过降低 T1DM 青少年的胰高血糖素和延迟胃排空来降低餐后高血糖。 动物研究显示 GLP-1 可以增加 β 细胞质量并减少细胞凋亡。 有关 GLP-1 在 T1DM 中使用的信息有限。 目前尚未有研究确定普兰林肽和艾塞那肽对 T1DM 血糖控制是否具有类似作用。 该提案的总体目标是制定针对胰高血糖素并改善 T1DM 血糖控制的安全有效的策略。 该提案的总体目标是制定针对胰高血糖素并改善儿童 T1DM 血糖控制的安全有效的策略。 方案 1 的具体目标是确定 T1DM 中艾塞那肽的降糖剂量，相当于我们为普兰林肽确定的剂量。 为此，17 名 T1DM 受试者将被随机分配到 4 项研究中，使用不同的普兰林肽剂量。 还将评估胰高血糖素抑制和胃排空延迟。 与较低剂量相比，较高剂量的艾塞那肽将对胃排空和胰高血糖素抑制产生更明显的影响。 具体目标 确定艾塞那肽的有效剂量，使餐后高血糖正常化而不引起低血糖。 确定艾塞那肽对胃排空和胰高血糖素抑制的影响。 该方案的长期目标是开发一种安全的艾塞那肽剂量，可用于新发 T1DM 患者。 将测试艾塞那肽的抗细胞凋亡特性，以确定在诊断早期使用艾塞那肽是否可以延长 β 细胞的存活时间，从而延长糖尿病的蜜月期。