CLINICAL TRIAL: A DOUBLE-BLIND STUDY TO EXPLORE EFFECTS OF LAF237 ON GLUCOSE DUR

临床试验：探索 LAF237 对葡萄糖 DUR 影响的双盲研究

• 批准号: 7718692
• 负责人: RALPH A DEFRONZO
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718692
• 关键词: Acute; Adult; Affect; Age; Antidiabetic Drugs; Appearance; Blood Glucose; Blood specimen; Cheese; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Diet; Dipeptidyl-Peptidase IV; Dose; Double-Blind Method; Drug Kinetics; Enzymes; Fasting; Flavoring; Funding; Furuncles; Gastrointestinal tract structure; Genetic Crossing Over; Glucagon; Glucose; Glucose Plasma Concentration; Glycosylated hemoglobin A; Goals; Grant; Health; Hepatic; Hypoglycemic Agents; Infusion procedures; Institution; Insulin; Intestines; Label; Lead; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Oral; Oranges; Patients; Placebos; Plasma; Production; Proinsulin; Randomized; Rate; Research; Research Personnel; Resources; Sampling; Source; Testing; Time; Translating; United States National Institutes of Health; Visit; Water; Work; blood glucose regulation; clinically relevant; diabetic; egg; glucagon-like peptide 1; glucose output; glucose production; improved; insulin secretion

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. OBJECTIVE: The primary objective of this study is to determine the effect of a single dose of LAF237 on the rate of appearance of endogenous glucose (RaE) during the overnight post-absorptive period in type 2 diabetics. Secondary objectives will determine: (1) the rate of disappearance of glucose during the overnight post-absorptive period; (2) the effect on fasting plasma glucose concentration; (3) effects on insulin secretion rates, glucagon levels, and rate of glucose entry from the GI tract; (4) if alterations in insulin and glucagon secretion affect plasma free fatty acid levels; and (5) the acute effects of LAF237 on the proinsulin/insulin ratio. RESEARCH PLAN/METHODS: This is a randomized, cross-over comparison study of the effect of LAF237 and placebo on endogenous glucose production. LAF237 is an investigational agent that blocks the enzyme dipeptidyl-peptidase-IV. This enzyme, DPP-4, is responsible for rapidly degrading glucagons-like peptide-1 (GLP-1) upon its release in the intestine after a meal. GLP-1 suppresses glucagons release, suppressing hepatic glucose output. Thus, if is expected that LAF237 should lead to increased GLP-1 levels, decreased glucagons production, and lower blood sugars. This translates into an improved glucose homeostasis for diabetics. Investigators will study adults ages 18-75 with type 2 diabetes, otherwise in good health, HbA1c at 7-11%, fasting blood sugar 160-280, diet- or oral hypoglycemic agent-controlled diabetes, and BMS 22 to 45. Subjects will be seen on the GCRC four times. During the second and third visits, patients will receive a meal-tolerance test consisting of a boiled egg, parmesan cheese, and orange-flavored water with C14-labeled glucose. In addition, they will receive an infusion of H3-labeled glucose, and serial blood samples for glucose pharmacokinetics (total samples up to 882 ml). The goal is to determine the pharmacokinetics of both the C14-labeled and H3-labeled glucose. CLINICAL RELEVANCE: LAF is a new oral antidiabetic agent that works by inhibiting DDP-IV, leading to inhibition of glucagon secretion and stimulation of insulin secretion. It can be used as monotherapy or in combination with currently approved antidiabetic agents.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：这项研究的主要目的是确定LAF237的单剂量对2型糖尿病患者的过夜后夜间吸收后期的内源性葡萄糖（RAE）的外观效果。 次要目标将确定：（1）在吸收后过夜的葡萄糖消失率； （2）对空腹血糖浓度的影响； （3）对胰岛素分泌速率，胰高血糖素水平和葡萄糖进入的影响； （4）如果胰岛素和胰高血糖素分泌的改变会影响血浆无脂肪酸水平； （5）LAF237对蛋白/胰岛素比的急性作用。 研究计划/方法：这是对LAF237和安慰剂对内源性葡萄糖产生影响的随机，交叉比较研究。 LAF237是阻断二肽基肽酶-IV酶的研究剂。 该酶（DPP-4）负责在进餐后释放到肠道后迅速降解葡萄糖样肽-1（GLP-1）。 GLP-1抑制葡萄糖释放，抑制肝葡萄糖输出。 因此，如果期望LAF237应导致GLP-1水平升高，葡萄糖产生降低和降低血糖。 这转化为改善糖尿病患者的葡萄糖稳态。 研究人员将研究18-75岁的成年人患有2型糖尿病，否则身体健康，HBA1C为7-11％，禁食血糖160-280，饮食或口服降糖药物控制糖尿病，BMS 22至45。 在第二次和第三次访问中，患者将接受耐餐测试，该测试包括煮鸡蛋，帕尔玛奶酪和带有C14标记葡萄糖的橙色水。 此外，它们将收到H3标记的葡萄糖和葡萄糖药代动力学的系列血液样本（总样品最高882 mL）。 目的是确定C14标记和H3标记的葡萄糖的药代动力学。 临床相关性：LAF是一种通过抑制DDP-IV来起作用的新口服抗糖尿病剂，从而导致胰高血糖素分泌和胰岛素分泌的刺激。 它可以用作单一疗法，也可以与当前批准的抗糖尿病药物结合使用。