Reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose

使用泛醇和/或 D-核糖减轻射血分数保留的心力衰竭患者的症状负担

• 批准号: 9378323
• 负责人: JANET Doreen PIERCE
• 金额: $ 57.95万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9378323
• 关键词: Activities of Daily Living; Address; Adenosine Triphosphate; Adult; Affect; Age; American Heart Association; Awareness; Behavioral; Behavioral Symptoms; Bioenergetics; Biological; Biological Markers; Blood; Brain natriuretic peptide; Cardiac; Cardiomyopathies; Caring; Cells; Cities; Clinical; Coenzyme Q10; Complex; Computer software; Data; Diastolic heart failure; Double-Blind Method; Dyspnea; EFRAC; Echocardiography; Edema; Exercise Tolerance; Exercise stress test; Exertion; Failure; Fatigue; Guidelines; Health Personnel; Health Status; Heart; Heart failure; Image; Impairment; Kansas; Knowledge; Left; Left Ventricular Ejection Fraction; Leg; Lower Extremity; Measurement; Measures; Mitochondria; Moods; Morbidity - disease rate; Muscle relaxation phase; Myocardial; Myocardium; Oral; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Perception; Performance; Play; Prevalence; Production; Publishing; Quality of life; Questionnaires; Randomized; Reactive Oxygen Species; Research; Research Personnel; Ribose; Role; Self Care; Self Efficacy; Sentinel; Severities; Shortness of Breath; Social Interaction; Swelling; Symptoms; Testing; Therapeutic Intervention; Venous; Ventricular; Walking; Work; alternative treatment; biobehavior; clinical practice; compare effectiveness; disabling symptom; effective therapy; exercise intolerance; experience; health related quality of life; heart function; improved; improved outcome; innovation; mortality; novel therapeutics; persistent symptom; personalized strategies; placebo controlled study; reduce symptoms; social; symptom management; symptom science; symptom treatment; treatment as usual; ubiquinol

ABSTRACT The prevalence of heart failure (HF) is increasing, and it is estimated that there will be 9.6 million U.S. adults who have HF by 2030. More than 50% of HF patients have a type of heart failure with preserved ejection fraction (HFpEF), also termed diastolic HF. The hallmark symptoms of HFpEF are lack of energy, fatigue, shortness of breath, exercise intolerance, and decreased quality of life. These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, patients with HFpEF suffer with severe lack of energy and other debilitating symptoms that affect their overall health-related quality of life. We have pilot data on patients with HFpEF showing that two supplements (ubiquinol and D-ribose) added to their usual HF care enhanced their myocardial energetics and diastolic function resulting in decreased symptom burden. Both ubiquinol (reduced form of coenzyme Q10) and D-ribose play a vital role in mitochondrial adenosine triphosphate (ATP) production. Thus, we propose a biobehavioral symptom science study using these two supplements (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Using a randomized, double-blind, placebo-controlled study, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. There are two aims. AIM 1: To determine the effects of oral ubiquinol, D-ribose, or a combination of the two administered over 12 weeks on symptoms accompanying low bioenergetics in patients with HFpEF. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The KCCQ includes five domains such as physical limitations, symptoms, self- efficacy, quality of life, and social interactions. AIM 2: To determine the effects of oral ubiquinol, D-ribose, or a combination of the two over 12 weeks on biological measures in patients with HFpEF. The 6-minute walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). These measures will determine if patients with HFpEF experience improved functional and clinical outcomes. Measures will be obtained at baseline, 6 weeks, and 12 weeks. The projected patient outcomes are improved health status, enhanced energy, increased 6-minute walking distance, improved cardiac performance, lower B-type natriuretic peptide, and increased ATP production. Improved clinical outcomes will enhance the patients' self- care activities of daily living, leading to better quality of life.

抽象的 心力衰竭（HF）的患病率正在增加，据估计将有960万美国成年人 到2030年患有HF。超过50％的HF患者具有一种心力衰竭，并保留了射血 分数（HFPEF），也称为舒张期HF。 HFPEF的标志性症状是缺乏能量，疲劳， 呼吸急促，运动不宽容和生活质量下降。这些患者的心脏受损 肌肉松弛和舒张期充气，研究人员与细胞能量障碍有关。 但是，当前的HF指南没有提供有效的治疗方法来解决这些潜在的病理生理 机制。因此，HFPEF患者严重缺乏能量和其他使人衰弱的症状 影响他们整体与健康相关的生活质量。我们有有关HFPEF患者的试点数据，表明两个 补充剂（泛醇和D-核糖）添加到通常的HF护理中，增强了他们的心肌能量和 舒张功能导致症状负担减轻。两种泛醇（辅酶Q10的降低形式）和 D-核糖在三磷酸腺苷（ATP）生产中起着至关重要的作用。因此，我们提出了一个 生物行为症状科学研究使用这两种补充剂（治疗干预措施）靶向 线粒体生物能量减少HFPEF患者经历的复杂症状。使用 随机，双盲，安慰剂对照研究，总体目标是确定是否施用 泛醇和/或D-核糖对HFPEF患者12周将降低其复合物的严重程度 症状并改善其心脏功能。有两个目标。目标1：确定口服的影响 泛素醇，D-核糖或两者的组合在12周内施用，伴随着低的症状 HFPEF患者的生物能学。用于评估患者对健康状况看法的措施 活力水平（能源）将是堪萨斯城的心肌病问卷（KCCQ）和活力子量表 情绪状态的特征。 KCCQ包括五个领域，例如身体限制，症状，自我 功效，生活质量和社会互动。目标2：确定口服泛醇，D-核糖或A的影响 在HFPEF患者的生物测量中，两周的组合在12周内合并。 6分钟的步行测试 将用于测试运动耐受性。左心室舒张功能将使用创新评估 高级超声心动图软件称为Speckle Tracking。我们将测量B型纳地尿肽 （从HF中的心室分泌）和乳酸/ATP比（细胞能量的度量）。这些措施将 确定HFPEF患者是否经历了改善功能和临床结果。措施将是 在基线，6周和12周时获得。预计的患者结果改善了健康状况， 增强能量，步行距离增加了6分钟，心脏性能提高，B型降低 亚钠肽，并增加了ATP的产生。改善的临床结果将增强患者的自我 日常生活的护理活动，从而带来更好的生活质量。