Cirrhosis, End-stage Liver Disease (ESLD), Liver Transplant, Poor Physical Fitness, Portal Hypertension, Sarcopenia
Conditions
Brief summary
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.
Interventions
OTHERNutritional consultation
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
BEHAVIORALPhysical training program
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.
BEHAVIORALBehavioral modification therapy
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.
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physical Fitness - VO2 | Change from Baseline to 12 weeks after baseline | Peak VO2 will be obtained from cardiorespiratory stress test |
| Physical Fitness - Distance Walked | Change from Baseline to 12 weeks after baseline | Total distance walked during 6-minute walk test |
| Sarcopenia | Change from Baseline to 12 weeks after baseline | Total thigh muscle volume (cm\^3), as determined by CT-scan. |
Countries
United States
Participant flow
Recruitment details
227 Subjects were recruited from the UAMS liver transplant clinic. 207 were excluded for meeting exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Active (Physical Training Program) physical activity + behavioral therapy + nutritional intervention
Nutritional consultation: 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
Physical training program: 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.
Behavioral modification therapy: 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. | 9 |
| Control nutritional intervention
Nutritional consultation: 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 | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | got liver transplant | 1 | 2 |
| Overall Study | had other surgery | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Active (Physical Training Program) | Control |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 9 | 56 years STANDARD_DEVIATION 7 | 54 years STANDARD_DEVIATION 11 |
| Albumin | 2.8 g/dL STANDARD_DEVIATION 0.5 | 3.1 g/dL STANDARD_DEVIATION 0.3 | 2.5 g/dL STANDARD_DEVIATION 0.6 |
| ALT | 39 units per liter STANDARD_DEVIATION 16 | 34 units per liter STANDARD_DEVIATION 18 | 45 units per liter STANDARD_DEVIATION 16 |
| Ascites | 13 Participants | 7 Participants | 6 Participants |
| AST | 65 units per liter STANDARD_DEVIATION 29 | 54 units per liter STANDARD_DEVIATION 28 | 78 units per liter STANDARD_DEVIATION 31 |
| BMI | 30 kg/m^2 STANDARD_DEVIATION 6 | 31 kg/m^2 STANDARD_DEVIATION 8 | 29 kg/m^2 STANDARD_DEVIATION 4 |
| Child-Turcotte-Pugh Class B | 11 Participants | 7 Participants | 4 Participants |
| Child-Turcotte-Pugh Class C | 6 Participants | 2 Participants | 4 Participants |
| Child-Turcotte-Pugh Score [median (range)] | 9 units on a scale | 9 units on a scale | 10 units on a scale |
| Creatinine | 0.9 mg/dL STANDARD_DEVIATION 0.2 | 0.8 mg/dL STANDARD_DEVIATION 0.3 | 0.9 mg/dL STANDARD_DEVIATION 0.3 |
| D'Amico Stage 4 | 15 Participants | 8 Participants | 7 Participants |
| D'Amico Stage 5 | 2 Participants | 1 Participants | 1 Participants |
| Diabetes Mellitus | 5 Participants | 4 Participants | 1 Participants |
| Esophageal varices | 12 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Etiology of cirrhosis-Alcoholic | 4 Participants | 4 Participants | 0 Participants |
| Etiology of cirrhosis-Cholestatic | 3 Participants | 1 Participants | 2 Participants |
| Etiology of cirrhosis-Hepatitis C | 5 Participants | 3 Participants | 2 Participants |
| Etiology of cirrhosis-NASH/cryptogenic | 5 Participants | 1 Participants | 4 Participants |
| Hemoglobin | 11.7 g/dL STANDARD_DEVIATION 2.4 | 12.1 g/dL STANDARD_DEVIATION 2.6 | 11.4 g/dL STANDARD_DEVIATION 2.3 |
| Hepatic encephalopathy | 17 Participants | 9 Participants | 8 Participants |
| Hypertension | 3 Participants | 1 Participants | 2 Participants |
| INR | 1.5 units on a scale STANDARD_DEVIATION 0.4 | 1.4 units on a scale STANDARD_DEVIATION 0.3 | 1.7 units on a scale STANDARD_DEVIATION 1.2 |
| Large volume paracentesis | 4 Participants | 3 Participants | 1 Participants |
| MELD-sodium | 17 units on a scale STANDARD_DEVIATION 4 | 16 units on a scale STANDARD_DEVIATION 4 | 19 units on a scale STANDARD_DEVIATION 3 |
| Platelets | 116 thousand platelets/microliter STANDARD_DEVIATION 63 | 121 thousand platelets/microliter STANDARD_DEVIATION 74 | 112 thousand platelets/microliter STANDARD_DEVIATION 24 |
| Prior variceal bleeding | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 6 Participants |
| Sodium | 135 mEq/L STANDARD_DEVIATION 3 | 135 mEq/L STANDARD_DEVIATION 3 | 135 mEq/L STANDARD_DEVIATION 4 |
| Total bilirubin (mg/dL) | 2.7 mg/dL STANDARD_DEVIATION 1.4 | 2.3 mg/dL STANDARD_DEVIATION 1.3 | 3.1 mg/dL STANDARD_DEVIATION 1.5 |
| Use of beta-blocker | 3 Participants | 1 Participants | 2 Participants |
| Weight | 91 kilograms STANDARD_DEVIATION 18 | 92 kilograms STANDARD_DEVIATION 21 | 89 kilograms STANDARD_DEVIATION 14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 |
Outcome results
Primary
Physical Fitness - Distance Walked
Total distance walked during 6-minute walk test
Time frame: Change from Baseline to 12 weeks after baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active (Physical Training Program) | Physical Fitness - Distance Walked | 59.2 meters |
| Control | Physical Fitness - Distance Walked | -91.4 meters |
p-value: 0.03ANCOVA
Primary
Physical Fitness - VO2
Peak VO2 will be obtained from cardiorespiratory stress test
Time frame: Change from Baseline to 12 weeks after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active (Physical Training Program) | Physical Fitness - VO2 | -1 mL oxygen/kg/min | Standard Deviation 6.5 |
| Control | Physical Fitness - VO2 | -3 mL oxygen/kg/min | Standard Deviation 6.5 |
p-value: 0.49ANCOVA
Primary
Sarcopenia
Total thigh muscle volume (cm\^3), as determined by CT-scan.
Time frame: Change from Baseline to 12 weeks after baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active (Physical Training Program) | Sarcopenia | -124 cubic centimeters |
| Control | Sarcopenia | -373 cubic centimeters |
p-value: 0.37ANCOVA