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

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

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis
• Intervention / Treatment: Other: Physical training; Other: Diet intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • DF
    • Mexico, DF, Mexico, 14000
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
    • Mexico, DF, Mexico, 14000
      • Instituto Nacional de Cardiologia Ignacio Chavez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Physical training - No encephalopathy; Patients randomized to the physical training program and diet intervention	Other: Physical training; A program of exercising under strict surveillance, with endurance and coordination maneuvers; Other Names: Exercise; Muscle ammonia metabolism; Other: Diet intervention; 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; Other Names: Diet; Nutritional therapy
ACTIVE_COMPARATOR: Control - No encephalopathy; Patients not allocated to exercise program, but undergoing diet intervention	Other: Diet intervention; 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; Other Names: Diet; Nutritional therapy
EXPERIMENTAL: Physical training - Early encephalopathy; Patients with early hepatic encephalopathy (minimal or clinical grade 1-2) randomized to the physical training program	Other: Physical training; A program of exercising under strict surveillance, with endurance and coordination maneuvers; Other Names: Exercise; Muscle ammonia metabolism; Other: Diet intervention; 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; Other Names: Diet; Nutritional therapy
ACTIVE_COMPARATOR: Control - Early encephalopathy; 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; 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; Other Names: Diet; Nutritional therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: Instituto Nacional de Cardiologia Ignacio Chavez
• Investigators: Study Chair: Sergio Ponce de Leon-Rosales, M.D., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran / Universidad Nacional Autonoma de Mexico; Study Chair: Florencia Vargas-Voráckova, MD, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán/ Universidad Nacional Autónoma de México

Publications and helpful links

General Publications

• Macias-Rodriguez RU, Ilarraza-Lomeli H, Ruiz-Margain A, Ponce-de-Leon-Rosales S, Vargas-Vorackova F, Garcia-Flores O, Torre A, Duarte-Rojo A. Changes in Hepatic Venous Pressure Gradient Induced by Physical Exercise in Cirrhosis: Results of a Pilot Randomized Open Clinical Trial. Clin Transl Gastroenterol. 2016 Jul 14;7(7):e180. doi: 10.1038/ctg.2016.38.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): January 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: August 16, 2007
• First Submitted That Met QC Criteria: August 16, 2007
• First Posted (ESTIMATE): August 17, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: CIIBH-Ref.1639/GAS 166-09/11-1