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Completed

NCT Number: NCT06288828

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

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).

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Key information

Conditions

Cirrhosis Aerobic Exercises Atrophy Autonomic Dysfunction Autonomic Nervous System Autonomic Nervous System Diseases Behavior Endothelial Function Fibrosis Flow Mediated Dilation Heart Rate Variability Lifestyle Modification Motor Activity Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathologic Processes Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Physical Activity Physical Functional Performance Physical Inactivity Primary Dysautonomias Sarcopenia Sedentary Behavior Signs and Symptoms

Age range

45 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Faculty of medicine, King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

About this study

An additional non-invasive assessment, Mesenteric Duplex Doppler Ultrasound, will be performed to evaluate mesenteric and portal blood flow as an exploratory parameter.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

Aerobic exercise + Nutrition consultant

Behavioral

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.

Other names: Exercise group, Active group

Nutrition consultant

Behavioral

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.

Other names: diet

Primary outcomes

  1. Time-domain Heart Rate Variability (HRV) Parameters: SDNN and RMSSD and SDANN

    Time frame: Change from Baseline (week 0) at Week 16

    Heart rate variability (HRV) was assessed using a 15-minute resting ECG recording. This table reports three time-domain measures: 1) SDNN (Standard deviation of all NN intervals), 2) RMSSD (Root mean square of successive differences), and 3) SDANN (Standard deviation of the average NN intervals). These parameters reflect autonomic nervous system activity and cardiac vagal tone. All data are reported in milliseconds. Higher values indicate better autonomic regulation. Only these three time-domain parameters are presented in this table.

  2. Time Domain Outcome: pNN50

    Time frame: Change from Baseline (week 0) at week 16

    A time-domain measure of heart rate variability (HRV) reflecting parasympathetic activity. It is calculated as the percentage of successive normal-to-normal (NN) intervals that differ by more than 50 milliseconds. Data were collected using 3-lead ECG during a 15-minute resting period."

  3. HRV Frequency Domain Measures: TP, HF, LF, VLF

    Time frame: Change from Baseline (week 0) at Week 16

    Assessment of frequency-domain components of heart rate variability, including Total Power (TF), High Frequency (HF), Low Frequency (LF), and Very Low Frequency (VLF). Analysis was performed using Adinstrument (tm) on a 15-minute ECG recording at rest. These parameters reflect the power distribution across different frequency bands and represent autonomic nervous system activity. Data presented in the table represent the change from baseline to Week 16.

  4. Changes in Ewing Autonomic Battery Test Scores (Improved, No Change, Worsened)

    Time frame: Change from Baseline (week 0) and Week 16

    Categorical assessment of changes in autonomic function using the Ewing Autonomic Battery test. Participants are classified into three categories: 'Improved', 'No change', or 'Worsened' based on their composite score changes from baseline to Week 16. Results are reported as the number of participants in each category.

  5. Endothelial Function Test: Change in Flow-mediated Dilation (FMD)

    Time frame: Change from Baseline (week 0) at Week 16

    Assessment of the change in brachial artery flow-mediated dilation (FMD) from baseline to Week 16. FMD was determined by ultrasound as the percentage increase in arterial diameter during reactive hyperemia compared to baseline diameter. Results are reported as the percentage change (%). Positive values indicate an improvement in endothelial-dependent vasodilation.

  6. HRV Frequency Domain Measures: Low Frequency/High Frequency (LF/HF) Ratio

    Time frame: Change from baseline (week 0) to week 16

    The LF/HF ratio is calculated as the ratio between the absolute power of the Low Frequency (LF) and High Frequency (HF) bands. It is used as an index of sympathovagal balance. Results are reported as a ratio (unitless).

Secondary outcomes

  1. Muscle Mass Change

    Time frame: Change from Baseline (week 0) at week 16

    Lean appendicular mass (kg) from Dual energy X-ray absorptiometry (DXA)

  2. Physical Function

    Time frame: Change from Baseline (week 0) at week 16

    6-minute walk test (minute)

  3. Muscle Strength Change

    Time frame: Change from Baseline (week 0) at week 16

    Handgrip strength (kg) from dynamometer

  4. Splanchnic Volume Flow

    Time frame: Baseline and after 16-week intervention

    Blood-flow parameters derived from mesenteric Doppler ultrasound (celiac and superior mesenteric arteries, portal vein) were obtained as exploratory markers of splanchnic circulation.

  5. The Association Between Changes in Muscle Mass and Changes in Serum Ammonia Levels

    Time frame: Baseline and Week 16

    Assessment of the correlation between the change in appendicular muscle mass index (measured by appendicular mass divided by height squared via Dual-Energy X-ray Absorptiometry; DXA) and the change in serum ammonia levels from baseline to week 16. Statistical significance is evaluated using Spearman's rank correlation coefficient for non-normally distributed data.

Sponsors and collaborators

Lead sponsor

King Chulalongkorn Memorial Hospital

Other

Collaborators

  • Chulalongkorn University

Registry information

Official study title

The Efficacy Of Aerobic Exercise Training On Autonomic Nervous System And Endothelial Function In Patients With Compensated Cirrhosis: A Parallel, RCT Study

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Mar 1, 2024
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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