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: 8166983
• 负责人: RICHARD E PRATLEY
• 金额: $ 7.1万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166983
• 关键词: 2,4-thiazolidinedione; Address; Adipocytes; Affect; Antidiabetic Drugs; Blood Glucose; Blood specimen; Body fat; Bone Density; Brain; 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。 背景：肠促胰岛素激素是肠道响应食物摄入而产生的激素。 这些激素帮助身体控制葡萄糖（糖）的代谢。 特别是，两种肠促胰岛素激素（GLP-1 和 GIP）会导致胰腺分泌更多胰岛素以应对高血糖水平。 这有助于身体更有效地代谢葡萄糖，降低血糖水平。 除了对胰腺有影响外，GLP-1 和 GIP 对其他组织也有影响，包括大脑、肠道、脂肪细胞和骨骼。 一类新型口服药物被开发用于治疗 2 型糖尿病 (T2DM)，称为 DPP-4 抑制剂，通过防止 GLP-1 和 GIP 的分解来提高体内活性形式的 GLP-1 和 GIP 的水平。 本研究测试了常用于治疗 T2DM 的此类药物西他列汀 (Januvia) 是否会影响 T2DM 患者的骨转换标志物。 方法：为了解决这个问题，我们将招募通过饮食+运动或二甲双胍（另一种常用于治疗 T2DM 的药物）控制糖尿病的 T2DM 患者。 受试者将通过 DEXA 扫描和 3 小时混合膳食测试测量身体脂肪和骨矿物质密度。 在混合膳食测试期间，将采集血样来测量GLP-1和GIP的产生量。 还将在混合膳食测试期间获得的血液样本中测量骨形成标志物。 然后，受试者将被随机分配接受为期 8 周的西他列汀（100 毫克/天）或匹配的安慰剂（不含药物的非活性药片）治疗。 开始治疗后 4 周将对受试者进行观察，以评估安全性和耐受性。 治疗8周后，将重复膳食测试。 然后，受试者将在 1 周内停止初始治疗（西他列汀或安慰剂）（也就是说，在此期间他们将不再接受研究药物）。 洗脱期结束后，他们将开始使用其他研究药物进行第二个 8 周的治疗（也就是说，如果他们最初接受西他列汀，他们将在第 2 阶段接受安慰剂，反之亦然）。 第 2 阶段结束时，受试者将接受第三次混合膳食测试，测量 GLP-1、GIP 和骨转换标志物。 意义：最近的研究表明，噻唑烷二酮类口服抗糖尿病药物，如罗格列酮（Avandia）和吡格列酮（Actos），可能会削弱骨骼，增加老年糖尿病女性骨折的风险。 拟议的研究将测试 DPP-4 抑制剂类药物，例如西格列汀 (Januvia)，是否通过增加 GLP-1 和 GIP 的活性对骨转换产生有益影响。 这项试点研究的结果可能表明需要进行更长期的研究，以确定 DPP-4 抑制剂是否可以增加糖尿病患者的骨矿物质密度并降低骨折风险。