Effect of Physical Training Program on Health-related Quality of Life in Cirrhosis

Study Overview
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Brief Summary
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Physical training improves quality of life (QOL) in non-hepatic diseases. It is possible that the same effect happens in patients with cirrhosis and portal hypertension. Hepatic encephalopathy may also benefit from physical activity by increasing ammonia metabolism. The intention of this study is to assess if patients can improve their QOL and hepatic encephalopathy during a physical training program, and to address its safety.

Detailed Description
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Patients with cirrhosis and portal hypertension experience a marked deterioration in health-related quality of life (QOL), as it has been shown with the use of questionnaires such as Short-Form-36 (SF-36) and Chronic Liver Disease Questionnaire (CLDQ). The deterioration in QOL is progressively accentuated as liver failure advances. There is a positive association between the level of physical activity and the sense of QOL, and physical training programs have proved to be useful in improving QOL in cardiovascular and pulmonary diseases, and in conditions affecting cognition. Thereby, it is hypothesized that a physical training program may improve QOL and hepatic encephalopathy in patients with cirrhosis and portal hypertension. Data supporting physical activity as a way to improve hepatic encephalopathy derives from experimental models showing that skeletal muscle is able to remove blood ammonia, presumably by inducing the enzyme glutamine synthetase. However, it is uncertain whether such a program is safe, or if it can lead to an increase in portal hypertension and progression of the disease.

Official Title
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Impact and Safety of a Physical Training Program on Health-related Quality of Life in Patients With Cirrhosis and Portal Hypertension

Conditions
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Cirrhosis

Intervention / Treatment
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* Other: Physical training
* Other: Diet intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven or clinically evident cirrhosis Able to perform exercise Exclusion Criteria: Overt hepatic encephalopathy grades 3 or 4 Cardiovascular complications (pulmonary hypertension, heart failure) Diabetes mellitus and microangiopathic complications, or under treatment with insulin Renal failure Portal hypertension with high risk for variceal bleeding Hepatocellular carcinoma

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physical training - No encephalopathy<br>Patients randomized to the physical training program and diet intervention | Other: Physical training<br>* A program of exercising under strict surveillance, with endurance and coordination maneuvers<br>* Other names: Muscle ammonia metabolism;Other: Diet intervention<br>* Energy intake tailored to basal metabolism and level of physical activity. Protein and sodium intake will be adjusted to 1.2-1.5 g/kg/d, and 1.5-2 g/d of salt, respectively. The latter will be adjusted only in those patients presenting ascites and/or edema<br>* Other names: Diet;|
| Active Comparator: Control - No encephalopathy<br>Patients not allocated to exercise program, but undergoing diet intervention | Other: Diet intervention<br>* Energy intake tailored to basal metabolism and level of physical activity. Protein and sodium intake will be adjusted to 1.2-1.5 g/kg/d, and 1.5-2 g/d of salt, respectively. The latter will be adjusted only in those patients presenting ascites and/or edema<br>* Other names: Diet;|
| Experimental: Physical training - Early encephalopathy<br>Patients with early hepatic encephalopathy (minimal or clinical grade 1-2) randomized to the physical training program | Other: Physical training<br>* A program of exercising under strict surveillance, with endurance and coordination maneuvers<br>* Other names: Muscle ammonia metabolism;Other: Diet intervention<br>* Energy intake tailored to basal metabolism and level of physical activity. Protein and sodium intake will be adjusted to 1.2-1.5 g/kg/d, and 1.5-2 g/d of salt, respectively. The latter will be adjusted only in those patients presenting ascites and/or edema<br>* Other names: Diet;|
| Active Comparator: Control - Early encephalopathy<br>Patients with early hepatic encephalopathy (minimal or clinical grades 1-2) not allocated to the physical training program, but undergoing diet intervention | Other: Diet intervention<br>* Energy intake tailored to basal metabolism and level of physical activity. Protein and sodium intake will be adjusted to 1.2-1.5 g/kg/d, and 1.5-2 g/d of salt, respectively. The latter will be adjusted only in those patients presenting ascites and/or edema<br>* Other names: Diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in QOL questionnaires | QOL will be measured by means of SF-36 and CLDQ | 3 months | 
| Lack of deterioration in portal hypertension | This will be measured by the hepatic vein pressure gradient (HVPG) through liver catheterization | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in cognitive status | This outcome will be evaluated with neuropsychological tests: psychometric hepatic encephalpathy score (PHES) and the critical flicker frequency test (CFF) | 3 months | 
| No increase in the rate of variceal bleeding and no progression in the number/size of esophageal varices | History taking, hemoglobin measurement, and endoscopy for a detailed description regarding number and size of esophageal varices | 3 months | 
| Improved ammonia metabolism and decrease in oxidative stress | Ammonia, glutamine, glutamate, and glutamine synthetase determinations, as well as oxidative carbonylation of protein | 3 months | 
| Improvement in physical capacity and exercise tolerance | Metabolic equivalents (METs) achieved in the treadmill test | 3 months |