Safety, Tolerability and Efficacy of Coenzyme Q10 in Hemodialysis Patients

辅酶 Q10 在血液透析患者中​​的安全性、耐受性和有效性

• 批准号: 7849488
• 负责人: Jonathan Himmelfarb
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849488
• 关键词: Accounting; Address; Aldehydes; Anabolism; Antioxidants; Atherosclerosis; Biochemistry; Biological Assay; Biological Markers; Biology; Cardiac Death; Cardiovascular Diseases; Cardiovascular system; Chronic; Chronic Kidney Failure; Clinical; Clinical Trials; Coenzyme Q10; Complementary therapies; Congestive Heart Failure; Couples; Data; Death Rate; Depressed mood; Dialysis patients; Dialysis procedure; Dose; Electron Transport; Future; General Population; Hemodialysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hydroxymethylglutaryl-CoA reductase; Inflammation; Isoprene; Kidney; LDL Cholesterol Lipoproteins; Laboratories; Lead; Life Expectancy; Lipid Peroxidation; Medical; Metabolic; Metabolism; Mitochondria; Modeling; Morbidity - disease rate; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Pathogenesis; Patients; Plasma; Population; Population Study; Renal function; Risk Factors; Risk Reduction; Safety; Secondary to; Stroke; Sulfhydryl Compounds; Surrogate Markers; Testing; Therapeutic; United States; Uremia; antioxidant therapy; atorvastatin; base; cardiovascular pharmacology; cardiovascular risk factor; design; diabetic; dietary supplements; improved; mortality; multidisciplinary; novel strategies; nutrition; prognostic; public health relevance; sound

DESCRIPTION (provided by applicant): There are currently more than 300,000 patients receiving chronic dialysis therapy in the United States, and it is estimated that this population will rapidly rise to over 600,000 patients by 2010 and over 2,000,000 patients by 2030. Life expectancies for dialysis patients are only 1/3 to 1/6 of those of the general population with cardiovascular disease accounting for approximately 50% of mortality. At present, there are no therapies proved to lower the risk for cardiovascular morbidity and mortality in the dialysis population. Conventional cardiovascular risk factors exemplified in the Framingham Study have limited prognostic value in dialysis patients, suggesting that "non-traditional" risk factors influenced by the uremic metabolic milieu may be particularly important. Increased oxidative stress contributes to the pathogenesis of atherosclerosis and uremia has recently been identified as an increased oxidative stress state. Coenzyme Q10, a readily available dietary supplement frequently used as an alternative and complementary therapy is a potent lipophilic antioxidant that couples electron transport to oxidative phosphorylation in the mitochondria. Coenzyme Q10 administration has been associated with significant clinical benefits in the treatment of congestive heart failure and improves endothelial function in patients with type II diabetes mellitus and preserved kidney function. Plasma concentrations of coenzyme Q10 appear to reflect net overall metabolic demand, and our preliminary data demonstrates that plasma coenzyme Q10 levels are depressed in hemodialysis patients, suggesting that coenzyme Q10 may be an ideal antioxidant for these patients. The central hypothesis of this application is that administration of coenzyme Q10 as a targeted antioxidant therapy will be safe and well tolerated, and will ameliorate the excessive oxidative stress burden in hemodialysis patients. This in turn will lead to improvements in surrogate markers for cardiovascular risk. We propose to test this hypothesis through the following Specific Aims: A.1. To determine the safety and tolerability of different doses of dietary supplement coenzyme Q10 in hemodialysis patients. A.2. To test the effect of the dietary supplement coenzyme Q10 on biomarkers of oxidative stress, systemic inflammation and endothelial function in hemodialysis patients. PUBLIC HEALTH RELEVANCE: Patients receiving chronic dialysis therapy have a high death rate due to cardiovascular disease. This project seeks to test whether administration of coenzyme Q10, a readily available dietary supplement, could result in clinical benefits for dialysis patients. This study is also designed to test whether administration of coenzyme Q10 to dialysis is safe and well-tolerated.

描述（申请人提供）：目前美国有超过30万患者接受慢性透析治疗，预计到2010年这一人群将迅速增加到60万以上，到2030年将超过200万。透析患者的预期寿命只有心血管疾病普通人群的1/3至1/6，心血管疾病约占50%死亡率。目前，尚无任何疗法被证明可以降低透析人群心血管发病率和死亡率的风险。弗雷明汉研究中举例说明的传统心血管危险因素对透析患者的预后价值有限，这表明受尿毒症代谢环境影响的“非传统”危险因素可能特别重要。氧化应激增加导致动脉粥样硬化的发病机制，而尿毒症最近被确定为氧化应激状态增加。辅酶 Q10 是一种现成的膳食补充剂，经常用作替代和补充疗法，是一种有效的亲脂性抗氧化剂，可将电子传输与线粒体中的氧化磷酸化结合起来。辅酶 Q10 给药在充血性心力衰竭的治疗中具有显着的临床益处，并可改善 II 型糖尿病患者的内皮功能并保留肾功能。辅酶 Q10 的血浆浓度似乎反映了净总体代谢需求，我们的初步数据表明，血液透析患者的血浆辅酶 Q10 水平较低，表明辅酶 Q10 可能是这些患者的理想抗氧化剂。该申请的中心假设是，辅酶Q10作为靶向抗氧化疗法的施用将是安全且耐受性良好的，并且将改善血液透析患者的过度氧化应激负担。这反过来将导致心血管风险替代标志物的改善。我们建议通过以下具体目标来检验这一假设：A.1。确定血液透析患者不同剂量膳食补充剂辅酶 Q10 的安全性和耐受性。 A.2.测试膳食补充剂辅酶 Q10 对血液透析患者氧化应激、全身炎症和内皮功能生物标志物的影响。 公共卫生相关性：接受长期透析治疗的患者因心血管疾病而死亡率很高。该项目旨在测试服用辅酶 Q10（一种现成的膳食补充剂）是否能为透析患者带来临床益处。这项研究还旨在测试辅酶 Q10 进行透析是否安全且耐受性良好。