The Efficacy of Aerobic Exercise Training on ANS and Endothelial Function in Compensated Cirrhosis

Summary

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:

1. 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.
2. Sarcopenia-related measures: Muscle mass (DEXA, BIA), muscle strength (handgrip dynamometry), and physical performance (6-minute walk test).
3. Laboratory outcomes: Serum ammonia, liver function tests, fasting glucose, albumin, renal function, and coagulation profile.
4. Correlative analyses: Associations between (a) muscle mass and serum ammonia, and (b) muscle mass and autonomic parameters (e.g., HRV indices).

Conditions

• Cirrhosis
• Aerobic Exercises
• Lifestyle Modification
• Endothelial Function
• Autonomic Nervous System
• Autonomic Dysfunction
• Heart Rate Variability
• Flow Mediated Dilation
• Sarcopenia
• Physical Activity
• Physical Functional Performance
• Physical Inactivity

Interventions

BEHAVIORAL

Aerobic exercise + Nutrition consultant

Participants in the intervention group will engage in 150 minutes of moderate aerobic exercise weekly for 16 weeks, primarily brisk walking or jogging. For the initial four weeks, they will visit the hospital weekly for guidance and participate in home-based exercise following a protocol totaling 150 minutes of moderate aerobic exercise in the form of brisk walking or jogging. Healthcare professionals will help adjust exercise intensity based on heart rate (60-80% of maximum) and perceived exertion (RPE 12-15), while monitoring vital signs and adverse events. After, they will transition to a home exercise program for twelve weeks, recording exercise details in a logbook. Weekly follow-up calls will ensure adherence and monitor adverse events. They will be provided with nutritional recommendations by a dietitian, the same as the control group.

BEHAVIORAL

Nutrition consultant

Participants will maintain their physical activity at the same level as before enrolling in the study. However, they will be provided with nutritional recommendations by a dietitian, which include 1.2 grams of protein per kilogram of ideal body weight daily and a calorie intake of 35 kilocalories per kilogram of ideal body weight per day. To assess adherence and make necessary adjustments, participants will complete a 3-day food record at the beginning of the study, at week 8, and at the end of the study at week 16. If participants encounter difficulties adhering to the recommended nutritional intake, the dietitian will provide additional guidance to help them meet the requirements.

Sponsors & Collaborators

• Chulalongkorn University

  collaborator OTHER

• King Chulalongkorn Memorial Hospital

  lead OTHER

Principal Investigators

• Sirinda Kittiprachakul · King Chulalongkorn Memorial

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

45 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-12

Primary Completion

2025-08-15

Completion

2025-09-30

Countries

• Thailand

Study Locations