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: 8074570
• 负责人: Jonathan Himmelfarb
• 金额: $ 23.17万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8074570
• 关键词: Accounting; Address; Aldehydes; Alternative Therapies; 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; 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30万名患者正在接受慢性透析治疗，预计到2010年，这一群体将迅速上升到超过60万名患者，到2030年将超过200万名患者。透析患者的预期寿命仅为普通人群的1/3至1/6，心血管疾病约占死亡率的50%。目前，在透析人群中，还没有被证明可以降低心血管发病率和死亡率的治疗方法。在Framingham研究中举例说明的常规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。氧化应激增加是动脉粥样硬化的发病机制之一，尿毒症最近被确认为氧化应激增加状态。辅酶Q10是一种容易获得的膳食补充剂，经常被用作替代和补充疗法，是一种强大的亲脂性抗氧化剂，将线粒体中的电子传递与氧化磷酸化偶联。辅酶Q10的应用在治疗充血性心力衰竭方面有显著的临床益处，并改善了II型糖尿病患者的内皮功能，但肾功能未受影响。血浆辅酶Q10的浓度似乎反映了总的净代谢需求，我们的初步数据显示，血液透析患者的血浆辅酶Q10水平受到抑制，这表明辅酶Q10可能是这些患者理想的抗氧化剂。这一应用的中心假设是，给予辅酶Q10作为一种靶向抗氧化剂治疗将是安全和耐受性良好的，并将改善血液透析患者过度的氧化应激负担。这反过来将导致心血管风险替代标记物的改善。我们建议通过以下具体目标来检验这一假设：a1.目的：探讨不同剂量辅酶Q10在血液透析患者中的安全性和耐受性。A.2.目的：探讨辅酶Q10对血液透析患者氧化应激、全身炎症和内皮功能等生物标志物的影响。 公共卫生相关性：接受慢性透析治疗的患者因心血管疾病死亡率较高。该项目旨在测试服用辅酶Q10，一种容易获得的膳食补充剂，是否可以为透析患者带来临床益处。这项研究还旨在测试辅酶Q10用于透析是否安全和耐受性良好。