Impact of Home-Based Aerobic and Resistance Training in Chronic Liver Disease: a Randomized Control Trial

NCT06892366 | Completed DMC

• 1 other identifier: BTG
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether home-based exercise interventions, including aerobic exercise (AE) and a combination of aerobic and resistance exercise (ARE), can improve physical and health-related outcomes in patients with chronic liver disease (CLD). The primary population includes adult patients with CLD experiencing complications such as sarcopenia, malnutrition, and fatigue. The main questions it aims to answer are: Does home-based ARE improve oxygen consumption, muscle strength, and physical frailty more effectively than AE or no exercise? Can home-based exercise reduce fatigue and improve quality of life and health-related behaviors? Researchers will compare the outcomes of three groups: Home-based AE group Home-based ARE group Control group (physical activity counselling) Participants will: Perform an 8-week home-based exercise program based on their group allocation (either AE or ARE). Undergo evaluations before and after the intervention, including: Oxygen consumption (via cardiopulmonary exercise testing) Muscle strength (using a hand dynamometer and respiratory muscle strength tests) Body composition (via bioelectrical impedance analysis and skinfold thickness measurements) Quadriceps muscle thickness and cross-sectional area (using muscle ultrasound) Muscle oxygenation Fatigue levels (using the Fatigue Severity Scale) Physical frailty (using the Liver Frailty Index) Quality of life (using the Chronic Liver Disease Questionnaire) Health-related lifestyle behaviors (using the Health-Promoting Lifestyle Profile II)

Conditions

Chronic Liver Disease and Cirrhosis

Keywords

end-stage liver disease; exercise; sarcopenia

Outcome Measures

Primary Outcomes (17)

• Peak Oxygen Consumption (VO₂ Max)

  Peak oxygen consumption (VO₂ Max) was measured using a Cardiopulmonary Exercise Test (CPET) conducted on a treadmill following the Modified Bruce Protocol. Ventilatory parameters were recorded breath-by-breath using a calibrated metabolic device (COSMED, Quark RMR, Rome, Italy) with an airtight face mask. The primary outcome was peak VO₂ (ml/min).

  Baseline and at 8 weeks.

• Relative Oxygen Consumption (VO₂/kg)

  Relative oxygen consumption (VO₂/kg) was measured as part of the Cardiopulmonary Exercise Test (CPET). The outcome was reported as VO₂/kg (ml/kg/min).

  Baseline and at 8 weeks.

• Anaerobic Threshold VO₂

  The anaerobic threshold was determined using ventilatory parameters recorded during the Cardiopulmonary Exercise Test (CPET). The outcome was reported as VO₂ at the anaerobic threshold (ml/min).

  Baseline and at 8 weeks.

• Muscle Oxygenation (SmO₂)

  Muscle oxygenation (SmO₂) was measured during the Cardiopulmonary Exercise Test (CPET) using a near-infrared spectroscopy (NIRS) monitor (Moxy, Fortiori Design LLC, Minnesota, USA). The NIRS sensor was placed on the dominant leg's vastus lateralis muscle, positioned between the lateral epicondyle of the femur and the greater trochanter. SmO₂ values were recorded at rest (pre-test), at the end of CPET, and during recovery. The final 30 seconds of data were averaged for analysis at each stage. The reported outcome was the minimum SmO₂ value (%).

  Baseline and at 8 weeks.

• Change in Muscle Oxygenation During Exercise (ΔSmO₂)

  The change in muscle oxygenation (ΔSmO₂) was calculated as the difference between SmO₂ at rest (pre-test) and SmO₂ at peak exercise. The reported outcome was ΔSmO₂ (%).

  Baseline and at 8 weeks.

• Muscle Oxygenation During Recovery

  Recovery SmO₂ was measured as the SmO₂ value recorded 1 minute after exercise cessation. The reported outcome was recovery SmO₂ (%).

  Baseline and at 8 weeks.

• Total Hemoglobin (THb)

  Total hemoglobin (THb) was measured using near-infrared spectroscopy (NIRS) during CPET. THb values were recorded at rest, at peak exercise, and during recovery. The final 30 seconds of data were averaged at each stage. The reported outcome was the peak THb value (g/dL).

  Baseline and at 8 weeks.

• Peripheral muscle strength

  Peripheral muscle strength was measured using a digital hand dynamometer (LaFayette Instrument Company, Lafayette, Indiana, USA). The device recorded force in kilograms (kg), Newtons, and pounds. Participants were instructed to perform maximum isometric contractions during testing. Measurements were conducted for various muscle groups in standardized positions, including quadriceps, hamstrings, hip extensors, hip flexors, shoulder abductors, shoulder flexors, and scapular adductors. The dynamometer was positioned appropriately for each muscle group, such as 1-2 cm above the malleoli for knee extensors or on the posterior thigh proximal to the knee for hip extensors. Results were recorded in kilograms and analyzed for strength comparison across time points.

  Baseline and at 8 weeks.

• Respiratory muscle strength

  Respiratory muscle strength was assessed indirectly by measuring maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) using a portable mouth pressure device (Micro RPM, Care Fusion, Rochester, UK). Results were recorded in cmH2O. MIP was measured from residual lung volume, requiring participants to perform maximum inspiratory effort against a closed airway for 1-3 seconds. MEP was measured from total lung capacity, requiring maximum expiratory effort for 1-3 seconds. The highest value among three attempts with less than 10% variability was recorded. MIP and MEP values were expressed as percentages of age- and gender-predicted reference values at baseline and after the intervention.

  Baseline and at 8 weeks.

• Fat Mass

  Fat mass was measured using Bioelectrical Impedance Analysis (BIA) (Bodystat QuadScan 4000, Bodystat Ltd., Douglas, Isle of Man, UK). The reported outcome was fat mass (kg).

  Baseline and at 8 weeks.

• Lean Body Mass

  Lean body mass was assessed using Bioelectrical Impedance Analysis (BIA). The reported outcome was lean body mass (kg).

  Baseline and at 8 weeks.

• Total Body Water

  Total body water was measured as part of Bioelectrical Impedance Analysis (BIA). The reported outcome was total body water (liters).

  Baseline and at 8 weeks.

• Intracellular and Extracellular Fluid

  Intracellular and extracellular fluid were evaluated using Bioelectrical Impedance Analysis (BIA). The reported outcomes were intracellular fluid (liters) and extracellular fluid (liters).

  Baseline and at 8 weeks.

• Phase Angle

  Phase angle, a marker of cell membrane integrity and general health, was measured using Bioelectrical Impedance Analysis (BIA). The reported outcome was phase angle (degrees).

  Baseline and at 8 weeks.

• Rectus Femoris Muscle Thickness

  The thickness of the rectus femoris muscle was measured using ultrasound imaging (Logiq 200 Pro Ultrasound Device, General Electric, Chicago, Illinois, USA). The ultrasound transducer was placed perpendicular to the long axis of the femur, at a location two-thirds of the distance between the anterior superior iliac spine and the patella. Minimal pressure was applied to avoid compression of the muscle tissue during imaging. The reported outcome was rectus femoris muscle thickness (cm).

  Baseline and at 8 weeks.

• Rectus Femoris Cross-Sectional Area

  The cross-sectional area of the rectus femoris muscle was measured using ultrasound imaging. The transducer placement and imaging procedure were standardized to ensure consistent measurements. The reported outcome was rectus femoris cross-sectional area (cm²).

  Baseline and at 8 weeks.

• Physical Frailty (Liver Frailty Index)

  Physical frailty was assessed using the Liver Frailty Index (LFI), calculated with the following formula: LFI Score = (-0.030 x grip strength) + (-2.529 x sit-to-stand time) + (-0.040 x balance time) + 6. LFI includes: Grip Strength: Measured with a hand dynamometer in kilograms (kg). Sit-to-Stand Test: Time (seconds) to complete five sit-to-stand repetitions without hand support. Balance Test: Total time (seconds) maintaining feet-together, semi-tandem, and tandem stances (maximum 30 seconds).

  Baseline and at 8 weeks.

Secondary Outcomes (3)

• Physical Activity Level (IPAQ)

  Baseline and at 8 weeks.

• Quality of Life (Chronic Liver Disease Questionnaire - CLDQ)

  Baseline and at 8 weeks.

• Health-Promoting Lifestyle Behaviors (HPLP-II)

  Baseline and at 8 weeks.

Study Arms (3)

Aerobic Exercise (AE) Group

EXPERIMENTAL

Participants in this group performed moderate-intensity aerobic exercises, primarily walking, three non-consecutive days per week for eight weeks. Exercise intensity was set at 40-60% of peak VO2 or based on perceived exertion (Borg 4-6) for those on beta-blockers. Sessions were monitored via video conferencing, and participants used smart wristbands for heart rate tracking.

Behavioral: Home-Based Aerobic Exercise Program

Aerobic and Resistance Exercise (ARE) Group

EXPERIMENTAL

Participants in this group performed a combination of aerobic and resistance exercises. Aerobic sessions followed the same protocol as the AE group (3 days/week). Resistance exercises were performed 2 additional days per week using elastic resistance bands calibrated to 40-50% of 1RM. Each resistance session included 3 sets of 10 repetitions for major muscle groups. All sessions were conducted and monitored remotely.

Behavioral: Home-Based Aerobic and Resistance Exercise (ARE) Group

Control Group

NO INTERVENTION

This group does not receive a structured exercise intervention. While they are monitored for daily step counts and encouraged to stay active, there is no specific intervention implemented.

Interventions

Home-Based Aerobic Exercise Program BEHAVIORAL

Aerobic Exercise (AE) Group This intervention consists of a home-based aerobic exercise program emphasizing moderate-intensity walking, tailored to 40-60% of peak VO2 or Borg Scale 4-6 for those on beta blockers. Distinctive features include real-time session supervision via video conferencing and heart rate monitoring with a smart wristband. This approach ensures remote guidance, personalized intensity, and participant safety throughout the 8-week program.

Aerobic Exercise (AE) Group

Home-Based Aerobic and Resistance Exercise (ARE) Group BEHAVIORAL

Participants engaged in a combined home-based aerobic and resistance exercise program. Aerobic sessions followed the same protocol as the AE group (3 days/week). Resistance training was performed 2 additional days per week using elastic resistance bands set at 40-50% of one-repetition maximum (1RM). Resistance exercises targeted major muscle groups, with each session consisting of 3 sets of 10 repetitions, and 1-3 minutes of rest between sets. All sessions were monitored and supervised remotely.

Aerobic and Resistance Exercise (ARE) Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being followed up for chronic liver disease or listed on the liver transplant waiting list at the Hacettepe University Department of Internal Medicine, Division of Gastroenterology.
• Owning and being able to use a smartphone.
• Aged between 18 and 70 years.
• Receiving primary prophylactic treatment for gastroesophageal varices.
• Willingness to participate in the study.

You may not qualify if:

• Inability to own or use a smartphone.
• Participation in an exercise training program within the last year.
• Previous liver transplantation.
• High-risk varices without beta-blocker treatment.
• Presence of persistent hepatic encephalopathy.
• Hepatic hydrothorax.
• Pulmonary vascular complications of portal hypertension.
• Chronic renal failure requiring dialysis.
• Hemoglobin level below 10 g/dL.
• Creatinine level above 2 mg/dL.
• Human Immunodeficiency Virus (HIV) infection.
• Presence of hepatocellular carcinoma (HCC).
• Recent acute myocardial infarction.
• Uncontrolled arrhythmias causing symptomatic hemodynamic instability.
• Contraindications to maximal exercise testing.

Sponsors & Collaborators

• Hacettepe University: lead

Study Sites (1)

Hacettepe University Faculty of Physical Therapy and Rehabilitation

Ankara, Altındağ, 06100, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Fibrosis; End Stage Liver Disease; Motor Activity; Sarcopenia

Interventions

Population Groups

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Behavior; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Naciye Vardar Yağlı, Prof

  Hacettepe University Faculty of Physical Therapy and Rehabilitation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: January 12, 2025
• First Posted: March 24, 2025
• Study Start: September 20, 2020
• Primary Completion: April 16, 2024
• Study Completion: June 16, 2024
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The individual participant data (IPD) will become available starting 6 months after the publication of the study's summary data or main results. The data will remain accessible for a period of 5 years following the initial availability date. Requests for access can be made during this time frame, subject to approval and adherence to institutional guidelines and ethical standards.
• Access Criteria: Individual participant data (IPD) and supporting information will be shared with researchers who provide a methodologically sound proposal for scientific analyses that align with the objectives of this study. Requests will be reviewed by an institutional review committee at Hacettepe University to ensure compliance with ethical standards and data protection regulations. Approved researchers will be required to sign a data use agreement outlining conditions for use, storage, and confidentiality. Data will be shared securely through encrypted digital platforms.

Locations

TU (1)