CLINICAL TRIAL: EFFECTS OF SITAGLIPTIN ON BONE TURNOVER IN PTS WITH TYPE 2 DIABE

临床试验：西他列汀对 2 型糖尿病患者骨转换的影响

• 批准号: 7952124
• 负责人: RICHARD E PRATLEY
• 金额: $ 2.15万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952124
• 关键词: 2,4-thiazolidinedione; Address; Adipocytes; Affect; Antidiabetic Drugs; Blood Glucose; Blood specimen; Body fat; Bone Density; Brain; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DEXA; Diabetes Mellitus; Eating; Fracture; Funding; GNAI2 gene; Glucose; Grant; Hormones; Hour; Institution; Insulin; Longitudinal Studies; Measurement; Measures; Medicine; Metformin; Methods; Non-Insulin-Dependent Diabetes Mellitus; Oral; Osteogenesis; Pancreas; Patients; Pharmaceutical Preparations; Pilot Projects; Pioglitazone; Placebos; Randomized; Recruitment Activity; Research; Research Personnel; Resources; Risk; Safety; Scanning; Source; Tablets; Takeda brand of pioglitazone hydrochloride; Testing; Thiazolidinediones; Tissues; United States National Institutes of Health; bone; bone turnover; diet and exercise; glucagon-like peptide 1; glucose metabolism; incretin hormone; inhibitor/antagonist; older women; prevent; response; rosiglitazone; sugar; treatment duration

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. Background: Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. In addition to their effects on the pancreas, GLP-1 and GIP have effects on other tissues, including the brain, gut, fat cells and bone. A new class of oral drugs developed for the treatment of type 2 diabetes mellitus (T2DM) called DPP-4 inhibitors increases levels of the active forms of GLP-1 and GIP in the body by preventing their breakdown. This study tests whether a medicine in this class called sitagliptin (Januvia), which is commonly used to treat T2DM, affects markers of bone turnover in patients with T2DM. Methods: To address this question, we will recruit patients with T2DM whose diabetes is controlled either diet+exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat and bone mineral density by DEXA scanning and a 3-hour mixed meal test. During the mixed meal test, blood samples will be taken to measure how much GLP-1 and GIP are produced. Markers of bone formation will also be measured in blood samples obtained during the mixed meal test. Subjects will then be randomly assigned to 8 weeks of treatment with either sitagliptin (100 mg/day) or matching placebo (an inactive tablet that does not contain medication). Subjects will be seen 4 weeks after commencing treatment to assess safety and tolerability. After 8 weeks of treatment, the meal test will be repeated. Subjects will then be washed off of their initial treatment (sitagliptin or placebo) for 1 week (that is, they will receive no study medication during this period). After the washout period, they will commence a second 8 week period of treatment with the other study medication (that is, if they received sitagliptin initially, they will receive placebo during period 2 and vice versa). At the end of period 2, subjects will undergo a third mixed meal test with measurement of GLP-1, GIP and markers of bone turnover. Significance: Recent studies suggest that oral antidiabetic medications of the thiazolidinedione class such as rosiglitazone (Avandia) and pioglitazone (Actos), may weaken bones, increasing the risk of fractures in older women with diabetes. The proposed study will test whether drugs of the DPP-4 inhibitor class, such as sitagliptin (Januvia), have beneficial effects on bone turnover by increasing the activity of GLP-1 and GIP. Results of this pilot study may suggest the need to perform longer-term studies to determine whether DPP-4 inhibitors increase bone mineral density and reduce the risk of fractures in patients with diabetes.

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。 背景：肠降血糖素激素是肠道响应食物摄入量产生的激素。 这些激素有助于人体控制葡萄糖（糖）的代谢。 特别是，两种泌尿素激素（GLP-1和GIP）会导致胰腺分泌更多的胰岛素，以响应高血糖水平。 这有助于人体更有效地代谢葡萄糖，从而降低血糖水平。 除了对胰腺的影响外，GLP-1和GIP还对包括大脑，肠道，脂肪细胞和骨骼在内的其他组织还具有影响。 开发了一种新的口服药物，用于治疗2型糖尿病（T2DM），称为DPP-4抑制剂，通过防止其分解来增加体内的活性GLP-1和GIP的水平。 这项研究测试了该类别中通常用于治疗T2DM的药物（Januvia）中的一种药物是否会影响T2DM患者的骨转换标记。 方法：为了解决这个问题，我们将招募患有T2DM的患者，其糖尿病受到饮食+运动或二甲双胍的控制（另一种通常用于治疗T2DM的药物）。 受试者将通过DEXA扫描和3小时的混合餐测试对体内脂肪和骨矿物质密度进行测量。 在混合膳食测试期间，将采用血液样本来测量产生多少GLP-1和GIP。 骨形成的标记也将在混合餐测试期间获得的血液样本中进行测量。 然后，受试者将被随机分配给西他列汀（100 mg/day）或匹配的安慰剂（不含药物的不活跃的片剂）的8周治疗。 开始治疗后4周，将看到受试者以评估安全性和耐受性。 经过8周的治疗后，将重复进餐测试。 然后，受试者将从初始治疗（西他列汀或安慰剂）中洗掉1周（也就是说，在此期间他们将不接受学习药物）。 在洗涤期之后，他们将开始使用其他研究药物进行第二次8周的治疗（也就是说，如果他们最初收到西他列汀，他们将在2期间接受安慰剂，反之亦然）。 在第2个时期结束时，受试者将通过测量GLP-1，GIP和骨转换标记的第三次混合餐测试。 意义：最近的研究表明，噻唑烷二酮类别的口服抗糖尿病药物，例如罗斯甘酸酮（Avandia）和吡格列酮（ACTOS），可能会削弱骨骼，增加糖尿病老年妇女骨折的风险。 拟议的研究将测试DPP-4抑制剂类药物（例如锡塔列汀（Januvia））是否通过增加GLP-1和GIP的活性对骨转换具有有益的影响。 这项试验研究的结果可能表明需要进行长期研究以确定DPP-4抑制剂是否会增加骨矿物质密度并降低糖尿病患者骨折的风险。