The Efficacy Of Aerobic Exercise Training On Autonomic Nervous System And Endothelial Function In Patients With Compensated Cirrhosis: A Parallel, RCT Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- 1.Autonomic function test: Heart rate variability (HRV), Ewing autonomic battery test
研究概览
简要总结
The goal of this randomized controlled trial is to investigate whether a 16-week structured aerobic exercise program combined with nutritional consultation can improve autonomic and endothelial function in patients with compensated cirrhosis.
Study Design:
This assessor-blinded, parallel-group randomized controlled trial will be conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Fifty adults with compensated (Child-Pugh class A) cirrhosis will be recruited during routine hepatology clinic visits. Eligible participants are aged 45-75 years, have a sedentary lifestyle (<150 minutes of moderate or <75 minutes of vigorous physical activity per week), and have abstained from alcohol for at least six months.
Exclusion criteria include active or recently treated hepatocellular carcinoma (within three months), severe portal hypertension complications (untreated large varices, prior variceal bleeding, or severe gastropathy), transjugular intrahepatic portosystemic shunt (TIPS), unstable cardiac disease, orthopedic limitations, morbid obesity (BMI >35 kg/m²), or current use of alpha- or beta-blockers that affect autonomic function.
Intervention:
Participants will be randomly assigned to either the intervention or control group. Both groups will receive nutritional consultation and individualized dietary guidance at baseline, week 8, and week 16. Nutritional goals are set at 35 kcal/kg/day and 1.2 g/kg/day of protein intake. If targets are unmet, the dietitian will provide individualized recommendations to support adequate intake.
The intervention group will participate in a 16-week aerobic exercise program consisting of brisk walking at moderate intensity (50-70% of maximal heart rate), totaling 150 minutes per week. The program includes two phases:
- Phase 1 (Weeks 1-4): Combined hospital-based (1 session per week) and home-based exercise under physical therapist supervision, with gradual intensity titration.
- Phase 2 (Weeks 5-16): Fully home-based exercise following prescribed intensity and frequency, with weekly follow-up via telephone or messaging to monitor adherence, safety, and exercise log completion.
The control group will maintain their usual physical activity levels while receiving the same schedule of nutritional consultations and weekly follow-up for monitoring compliance and adverse events.
Outcomes:
Primary outcomes include changes in autonomic and endothelial function after 16 weeks.
- Autonomic function will be assessed using the Ewing autonomic battery test (HR response to standing, deep breathing, and Valsalva maneuver; BP response to posture and sustained handgrip) and heart rate variability (HRV) indices (SDNN, RMSSD, LF/HF ratio).
- Endothelial function will be evaluated using flow-mediated dilation (FMD) of the brachial artery, analyzed via Cardiovascular Suite™ software to assess nitric oxide-dependent vasodilation.
Secondary outcomes include:
- Splanchnic hemodynamics: Changes in celiac and superior mesenteric artery (SMA) blood flow measured via mesenteric Doppler ultrasound (Vivid IQ, GE Healthcare). Time-averaged mean velocity (TAMV), vessel diameter, and blood flow will be recorded at baseline and post-intervention.
- Sarcopenia-related measures: Muscle mass (DEXA, BIA), muscle strength (handgrip dynamometry), and physical performance (6-minute walk test).
- Laboratory outcomes: Serum ammonia, liver function tests, fasting glucose, albumin, renal function, and coagulation profile.
- Correlative analyses: Associations between (a) muscle mass and serum ammonia, and (b) muscle mass and autonomic parameters (e.g., HRV indices).
详细描述
An additional non-invasive assessment, Mesenteric Duplex Doppler Ultrasound, will be performed to evaluate mesenteric and portal blood flow as an exploratory parameter.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The diagnosis of cirrhosis is confirmed either through liver biopsy ,and/or compatible features on ultrasonography/ computer tomography or magnetic resonance imaging.
- •The age range is between 45 and 75 years.
- •Participants are classified as Child Pugh score class A.
- •Participants report a physical inactivity, defined as engaging in physical activity for less than 150 minutes of moderate-intensity physical activity per week, or less than 75 minutes of vigorous-intensity physical activity per week, or an equivalent combination of both.
排除标准
- •Active hepatocellular carcinoma (HCC) or remission of HCC within the past 3 months.
- •Untreated large esophageal varices (EV) greater than F2 or history of upper gastrointestinal bleeding from portal hypertension or gastric varices.
- •Active or history of hepatic encephalopathy (HE).
- •Inpatient hospitalization for any reason or discharge from the hospital within the past 3 months.
- •Complete portal vein thrombosis.
- •Transjugular intrahepatic portosystemic shunt.
- •Contraindications to exercise, such as recent myocardial infarction, unstable angina, electrocardiography changes within the past 24 hours, complete heart block, acute congestive heart failure, uncontrolled hypertension, hemoglobin level less than 11 g/dL, platelet count less than 50,000 cells/mm 3 .
- •End-stage renal disease without dialysis.
- •Severe orthopedic problems that limit the ability to exercise.
- •Inability to communicate with the research team via telemedicine system.
- •Body mass index (BMI) exceeding 35 kg/m 2 .
- •On alpha or beta-blocker
研究组 & 干预措施
Exercise group
Participants in the intervention group will undergo 150 minutes of moderate aerobic exercise per week for 16 weeks, accompanied by a personalized nutritional plan (1.2 grams of protein per kilogram of ideal body weight per day and a calorie intake of 35 kilocalories per kilogram of ideal body weight per day).
干预措施: Nutrition consultant (Behavioral)
Exercise group
Participants in the intervention group will undergo 150 minutes of moderate aerobic exercise per week for 16 weeks, accompanied by a personalized nutritional plan (1.2 grams of protein per kilogram of ideal body weight per day and a calorie intake of 35 kilocalories per kilogram of ideal body weight per day).
干预措施: Aerobic exercise + Nutrition consultant (Behavioral)
Control group
The control group will solely receive nutritional guidance and maintain their physical inactivity.
干预措施: Nutrition consultant (Behavioral)
结局指标
主要结局
1.Autonomic function test: Heart rate variability (HRV), Ewing autonomic battery test
时间窗: The study duration will span from enrollment through treatment completion at 16 weeks or within 2 weeks after the end of the study
HRV: Time-domain: SDNN (milliseconds), SD of delta NN (milliseconds), o RMSSD, Mean spectrum NN (milliseconds), NN50 (%) Frequency-domain: Very Low-Frequency (VLF) Power, Low-Frequency (LF) Power, High-Frequency (HF) Power , LF/HF Ratio
Endothelial function test: Flow mediated dilation (FMD) in % FMD change
时间窗: The study duration will span from enrollment through treatment completion at 16 weeksor within 2 weeks after the end of the study
次要结局
- Physical function(The study duration will span from enrollment through treatment completion at 16 weeks, plus or minus 2 weeks".)
- Muscle mass change(The study duration will span from enrollment through treatment completion at 16 weeks, or within 2 weeks after the end of the study)
- Muscle strength change(The study duration will span from enrollment through treatment completion at 16 weeks, or within 2 weeks after the end of the study)
研究者
Sirinda Kittiprachakul
Principal Investigator
King Chulalongkorn Memorial Hospital