Exercise Training Decreases Alcohol Consumption and Tissue Injury by an FGF21-dependent Mechanism
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Alcohol Consumption Measured by Timeline Follow Back (TLFB)
研究概览
简要总结
This randomized study will examine whether a 12-week supervised home-based endurance exercise program can reduce alcohol use and alcohol craving in adults with alcohol use disorder (AUD) and alcohol-related liver disease (ALD). Thirty participants will be assigned in a 1:1 ratio to endurance exercise plus standard of care or standard of care alone. Participants in the exercise group will cycle at home three days per week for approximately 60 minutes per session with remote supervision. The study will also evaluate effects of exercise on FGF21, liver injury markers, exercise capacity, physical function, body composition, fatigue, skeletal muscle and mitochondrial function, and exploratory molecular and microbiome measures. The investigators hypothesize that endurance exercise will reduce alcohol use and craving while improving liver and skeletal muscle outcomes, potentially through an FGF21-related mechanism.
详细描述
Alcohol use disorder is a major driver of continued liver injury in alcohol-related liver disease. Patients with ALD also commonly develop sarcopenia, impaired skeletal muscle function, fatigue, mitochondrial dysfunction, reduced exercise capacity, and physical frailty. Exercise may improve muscle and metabolic function and may also reduce alcohol craving and consumption. FGF21 has been proposed as a mechanistic link among exercise, skeletal muscle, liver injury, metabolism, and alcohol-related behavior.
This is a randomized, controlled, unblinded study of 30 adults with AUD/ALD. Participants will be randomized 1:1 to endurance exercise plus standard of care (EE+SOC) or standard of care alone (SOC). Participants assigned to EE+SOC will complete a 12-week home-based supervised cycling program three days per week, with a target of approximately 60 minutes per session and intensity adjusted for safety, tolerance, and beta-blocker use. Exercise sessions will be remotely monitored, and fitness testing will occur at Cleveland Clinic. Participants in the SOC arm will continue usual clinical care and their usual physical activity without the structured exercise intervention.
The study will assess alcohol consumption and craving; circulating and skeletal muscle FGF21; liver injury measures; exercise capacity and physical performance; body composition; fatigue; skeletal muscle metabolism and mitochondrial function; and exploratory transcriptomic, proteomic, metabolomic, microbiome, amino acid, protein synthesis, TCA intermediate, and cell-signaling responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Adults age 18 years or older, of either sex.
- •Clinical diagnosis of alcohol use disorder (AUD) / alcohol-related liver disease (ALD).
- •Meets NIAAA hazardous-drinking criteria: at least 7 drinks/week for women or 14 drinks/week for men for more than 6 months, with ongoing alcohol use within 2 months of evaluation.
- •MELD score less than
- •Able to safely participate in exercise testing and endurance exercise.
- •Able to provide informed consent.
- •No concurrent renal, cardiac, pulmonary, cerebrovascular, or malignant illness that affects skeletal muscle mass; no diabetes mellitus; and no use of medications that affect skeletal muscle mass/protein turnover as described in the protocol, including anabolic steroids, high-dose corticosteroids, or anticoagulants.
排除标准
- •• Pedal edema above the ankle or grade 2 pedal edema.
- •Liver transplant.
- •Active malignancy.
- •Gastrointestinal bleed within the previous 4 weeks.
- •Hepatic encephalopathy within the previous 6 months.
- •Grade 2 or greater active esophageal varices.
- •Active infection.
- •Large ascites by clinical and/or imaging criteria.
- •Advanced cardiac disease (NYHA class 3 or 4) or advanced pulmonary disease (GOLD class 3 or 4).
- •Use of medications affecting muscle protein turnover, including corticosteroids, or medications used to prevent clotting.
- •Prior orthopedic surgery or chronic joint pain that, in the opinion of the PI, may inhibit participation.
- •INR greater than 1.7 or platelet count less than 60,000/mL.
- •Unable to provide informed consent; judged likely to be unable to perform exercise or unlikely to complete the study in the opinion of the investigators.
- •End-stage kidney disease defined as eGFR less than 15 mL/min/1.73 m² or dialysis.
- •Considered unsafe for exercise in the opinion of the PI.
- •Failure to pass the exercise stress test.
研究组 & 干预措施
Endurance Exercise
Participants will receive standard of care and complete a 12-week supervised home-based endurance exercise program using a recumbent exercise bike.
干预措施: Endurance Exercise (Behavioral)
Standard of Care
Participants will continue usual clinical care and their current pattern of physical activity and will not participate in the structured endurance exercise intervention
结局指标
主要结局
Change in Alcohol Consumption Measured by Timeline Follow Back (TLFB)
时间窗: Baseline to 12 weeks
Alcohol consumption will be assessed using the Timeline Follow Back (TLFB). The primary comparison is change over 12 weeks between the EE+SOC and SOC groups.
次要结局
- Change in Alcohol Cravings Measured by the Penn Alcohol Cravings Scale (PACS)(Baseline to 12 weeks)
研究者
Srinivasan Dasarathy
Principle Investigator
The Cleveland Clinic