The Efficacy of Aerobic Exercise Training on Autonomic Nervous System and Endothelial Function in Patients With Compensated Cirrhosis

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

The goal of this clinical trial is to explore the impact of a 16-week aerobic exercise regimen on the autonomic nervous system and endothelial function in patients with compensated cirrhosis who maintain sedentary lifestyles. The primary research question is:

1) What effect does 16 weeks of aerobic exercise have on changes in the autonomic nervous system and endothelial function in cirrhotic patients?

Additionally, the secondary research questions are:

1. How does a 16-week aerobic exercise program influence changes in muscle mass, muscle strength, and physical performance in cirrhotic patients?
2. Is there a correlation between muscle mass and parameters of the autonomic nervous system in cirrhotic patients?

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). The control group will solely receive nutritional guidance and maintain their sedentary lifestyle. The researchers will compare outcomes between these two groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Physical Activity; Cirrhosis; Sarcopenia; Heart Rate Variability; Physical Functional Performance; Lifestyle Modification; Autonomic Dysfunction; Endothelial Function; Autonomic Nervous System; Aerobic Exercises; Flow Mediated Dilation
• Intervention / Treatment: Behavioral: Aerobic exercise; Behavioral: Nutrition consultant

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sirinda Kittiprachakul; Phone Number: 66+863979908; Email: sirinda.ning@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Faculty of medicine, King Chulalongkorn Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The diagnosis of cirrhosis is confirmed either through liver biopsy or the presence of portal hypertension, evidenced by esophageal varices on endoscopy, ascites, and/or compatible features on ultrasonography.
• The age range is between 45 and 75 years.
• Participants are classified as Child Pugh score class A.
• Participants report a sedentary lifestyle, 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 .
• Use of Vitamin E and C supplements.
• 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 30 kg/m 2 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Behavioral: Aerobic exercise; Participants in the intervention group will engage in 150 minutes of moderate aerobic exercise weekly for 16 weeks, primarily brisk walking or jogging. They will follow a personalized nutritional plan: 1.2 grams of protein per kilogram of ideal body weight daily and 35 kilocalories per kilogram of ideal body weight daily. For the initial four weeks, they will visit the hospital weekly for guidance. Healthcare professionals will help adjust exercise intensity based on heart rate (60-80% of max) and perceived exertion (RPE 12-15), monitoring vital signs and adverse events. After, they will transition to a home exercise program for eight weeks, recording exercise details in a logbook. Weekly follow-up calls will ensure adherence and monitor adverse events.; Other Names: Active group; Exercise group; Behavioral: Nutrition consultant; Participants will be provided with a personalized nutritional plan by a nutritionist, which will involve consuming 1.2 grams of protein per kilogram of ideal body weight daily, while also maintaining 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 difficulty in adhering to the recommended nutritional intake, the nutritionist will offer additional guidance to help them meet the requirements. The primary objective of this nutritional plan is to ensure that participants receive adequate nutrition to support their exercise regimen and maintain their body weight throughout the study period.; Other Names: diet
Other: Control group; The control group will solely receive nutritional guidance and maintain their sedentary lifestyle. The researchers will compare outcomes between these two groups.	Behavioral: Nutrition consultant; Participants will be provided with a personalized nutritional plan by a nutritionist, which will involve consuming 1.2 grams of protein per kilogram of ideal body weight daily, while also maintaining 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 difficulty in adhering to the recommended nutritional intake, the nutritionist will offer additional guidance to help them meet the requirements. The primary objective of this nutritional plan is to ensure that participants receive adequate nutrition to support their exercise regimen and maintain their body weight throughout the study period.; Other Names: diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autonomic function test: Heart rate variability (HRV)	in form of parameter change: Time-domain methods- SDNN (milliseconds), SD of delta NN (milliseconds), o RMSSD, Mean spectrum NN (milliseconds), NN50 (%) Frequency method:	The study duration will span from enrollment through treatment completion at 16 weeks or within 2 weeks after the end of the study
Endothelial function test: Flow mediated dilation (FMD) in % FMD change		The study duration will span from enrollment through treatment completion at 16 weeksor within 2 weeks after the end of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical function	6-minute walk test (minute)	The study duration will span from enrollment through treatment completion at 16 weeks, plus or minus 2 weeks".
Muscle mass change	Lean appendicular mass (kg) from Dual energy X-ray absorptiometry (DXA)	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	Handgrip strength (kg) from dynamometer	The study duration will span from enrollment through treatment completion at 16 weeks, or within 2 weeks after the end of the study

Collaborators and Investigators

• Sponsor: King Chulalongkorn Memorial Hospital
• Collaborators: Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Estimated): March 5, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Endothelial function; Autonomic nervous system; Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Liver Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Fibrosis; Liver Cirrhosis; Sarcopenia; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: IRB0569/66

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Individual participant data that underlie the results reported in this article, after deidentification (text,tables,figures, and appendices) will be provided with anyone who wishes to access the data.

Study Protocol will also be provided with anyone who wishes to access the data.

Information regarding submitting proposals and accessing data may be found at https://rehabmed.md.chula.ac.th/research/.

• IPD Sharing Time Frame: The data will be begin 9 months and end 36 months following article publication.
• IPD Sharing Access Criteria: Share via E-mail on request Contact: sirinda.ning@gmail.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No