IMPROVING NITRIC OXIDE-DERIVED OXIDANTS USING TOSIGLITAZONE IN NON-DIABETIC D

使用托西格列酮改善非糖尿病 D 中一氧化氮衍生的氧化剂

• 批准号: 7608202
• 负责人: ANNE KANDERIAN
• 金额: $ 0.06万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608202
• 关键词: 2,4-thiazolidinedione; 3-nitrotyrosine; Chronic; Clinic; Computer Retrieval of Information on Scientific Projects Database; Dilated Cardiomyopathy; Disease Progression; Double-Blind Method; End Point; Functional disorder; Funding; Future; Grant; Heart failure; Inflammation; Institution; Insulin; Insulin Resistance; Left Ventricular Dysfunction; Metabolic; Myocardial perfusion; Nitric Oxide; Oxidants; Patients; Performance; Placebos; Play; Prevention strategy; Randomized; Relative (related person); Research; Research Design; Research Personnel; Resources; Role; Safety; Serum; Source; Stress; Syndrome; Thiazolidinediones; United States National Institutes of Health; Week; follow-up; improved; insulin sensitivity; non-diabetic; novel therapeutics; randomized placebo controlled trial; rosiglitazone; therapeutic target

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. Aim: The principal aim is to investigate the safety and efficacy of rosiglitazone in patients with non-diabetic dilated cardiomyopathy. We hypothesize that in these patients, rosiglitazone is safe and can reduce nitric oxide (NO) derived stress thereby improving endothelial dysfunction, left ventricular performance, and metabolic parameters. Background: Insulin resistance is more prevalent in dilated cardiomyopathy and may be related to endothelial dysfunction. Increased oxidant stress and inflammation may have been shown to play a role in the pathophysiology of heart failure as well as NO-derived oxidants such as nitrotyrosine. Thiazolidinediones (TZDs) are insulin-sensitizing agents that directly improve insulin sensitivity and endothelial function. However, there is a paucity of information regarding the safety and efficacy of these agents. Study Design: The study will be a double-blind, randomized, placebo-control trial. Patients from the Heart Failure clinic with chronic stable heart failure will be screened. 60 patients will be randomized to receive either rosiglitazone versus placebo. Follow-up will be conducted at 6-week, 3-month and 6-month. The primary endpoint is to determine the absolute and relative changes in serum nitrotyrosine levels. Significance: The potential for insulin resistance as a novel therapeutic target in patients with heart failure has broad implications. Pharmacologic reversal of insulin resistance via improvement of endothelial dysfunction may significantly delay disease progression by improving myocardial perfusion and viability. We believe that pharmacological therapy targeting the insulin resistance syndrome may play an important role in our future management and prevention strategies.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：探讨罗格列酮治疗非糖尿病扩张型心肌病的安全性和有效性。 我们假设，在这些患者中，罗格列酮是安全的，可以减少一氧化氮（NO）衍生的压力，从而改善内皮功能障碍，左心室功能和代谢参数。 背景：胰岛素抵抗在扩张型心肌病中更为普遍，可能与内皮功能障碍有关。 增加的氧化应激和炎症可能已被证明在心力衰竭的病理生理学中起作用，以及NO衍生的氧化剂如硝基酪氨酸。 噻唑烷二酮类（TZDs）是一种胰岛素增敏剂，可直接改善胰岛素敏感性和内皮功能。 然而，关于这些药物的安全性和有效性的信息很少。 研究设计：本研究将是一项双盲、随机、安慰剂对照试验。 将筛选来自心力衰竭诊所的慢性稳定型心力衰竭患者。 60例患者将随机接受罗格列酮或安慰剂治疗。 将在6周、3个月和6个月时进行随访。 主要终点是确定血清硝基酪氨酸水平的绝对和相对变化。 意义：胰岛素抵抗作为心力衰竭患者新的治疗靶点的潜力具有广泛的意义。 通过改善内皮功能障碍的胰岛素抵抗的药理学逆转可以通过改善心肌灌注和存活率显著延缓疾病进展。 我们相信，针对胰岛素抵抗综合征的药物治疗可能在我们未来的管理和预防策略中发挥重要作用。