A Physical Activity Program in End-state Liver Disease

Study Overview
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Brief Summary
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The primary aim of this study is to improve both physical fitness and sarcopenia of patients with ESLD who are potentially eligible for liver transplantation through a 12-week physical training program. Secondary aims will focus on changes in anthropometrics, body composition, quality of life, and metabolic profile. This is a randomized clinical trial including 50 patients, with half allocated to the active group (physical training program) and half to standard of care.

Official Title
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A Physical Activity Program in End-stage Liver Disease: Pilot Study Assessing Changes in Physical Fitness, Sarcopenia, and the Metabolic Profile

Conditions
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End-stage Liver Disease (ESLD), Liver Transplant, Sarcopenia, Poor Physical Fitness, Cirrhosis, Portal Hypertension

Intervention / Treatment
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* Other: Nutritional consultation
* Behavioral: Physical training program
* Behavioral: Behavioral modification therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40 to 70. Cirrhosis, any cause, defined as: Biopsy-proven. Two or more of the following: albumin <3.5 g/dL, International Normalized Ration (INR) >1.3, radiologic or endoscopic evidence of portal hypertension. Creatinine <2.0 mg/dL. Physiologic Model for End Stage Liver Disease (MELD) ≥10. Decompensated cirrhosis with active or history of variceal bleeding, ascites, hepatic encephalopathy, or jaundice. Potential transplant candidate as per UAMS criteria Exclusion Criteria: Large gastric or esophageal varices with contraindication to use beta-blockers. Persistent hepatic encephalopathy grades 2-4. Prior diagnosis of hepatocellular carcinoma, or hepatic hydrothorax (with prior repeated thoracocentesis). Cirrhotic cardiomyopathy or congestive heart failure, pulmonary vascular complications, known active coronary artery disease, syncope, and cardiac dysrhythmias. Physical impediment to perform a cardiorespiratory fitness test. Use of implantable defibrillator or a pacemaker.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active (physical training program)<br>physical activity + behavioral therapy + nutritional intervention | Other: Nutritional consultation<br>* Dietary advice will be provided at the beginning of the study and individually tailored to the participant's usual eating habits plus amino acid supplement including 10 grams of branched-chain amino acids<br>Behavioral: Physical training program<br>* Physical activity prescription will target ≥10,000 steps/day, taking into account all activities performed throughout the day, although the increment in activity should be no less than 3000 steps/day above the baseline.<br>Behavioral: Behavioral modification therapy<br>* The behavior modification theory will be applied in the form of a structured set of cues and questions between investigator and participant at each visit in order to provide individually tailored counseling to enhance internal motivation and facilitate behavior change toward physical activity and dietary improvement that are adaptable to each participant's usual habits.<br>|
| Active Comparator: Control<br>nutritional intervention | Other: Nutritional consultation<br>* Dietary advice will be provided at the beginning of the study and individually tailored to the participant's usual eating habits plus amino acid supplement including 10 grams of branched-chain amino acids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Fitness - VO2 | Peak VO2 will be obtained from cardiorespiratory stress test | Change from Baseline to 12 weeks after baseline | 
| Physical Fitness - Distance Walked | Total distance walked during 6-minute walk test | Change from Baseline to 12 weeks after baseline | 
| Sarcopenia | Total thigh muscle volume (cm^3), as determined by CT-scan. | Change from Baseline to 12 weeks after baseline |