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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)
This randomized controlled trial was designed to evaluate the effects of an 8-week home-based exercise program on physical and health-related outcomes in patients with Chronic Liver Disease (CLD). The study included three groups: Aerobic Exercise (AE), Aerobic and Resistance Exercise (ARE), and a control group. Below are the details of the interventions and measurement techniques utilized in the study.
Study Groups and Interventions
Aerobic Exercise (AE) Group:
Exercise Protocol: Participants engaged in moderate-intensity walking exercises three non-consecutive days per week. The intensity was set at 40-60% of peak VO2 (measured by cardiopulmonary exercise testing), or based on the perceived exertion scale (Borg 4-6) for those on beta-blockers.
Session Structure:
Monitoring and Equipment: Heart rate monitoring was performed using Mi Smart Band 4. Sessions were conducted via video conferencing through WhatsApp, and pre-, during, and post-exercise feedback was recorded regarding heart rate, fatigue, and dyspnea.
Safety Measures: Participants exercised in a safe indoor space cleared of obstacles, using appropriate footwear.
Aerobic and Resistance Exercise (ARE) Group:
Exercise Protocol: Participants followed a combined regimen:
Aerobic exercises (3 days/week) were conducted following the AE protocol. Resistance training (2 days/week) was performed with elastic resistance bands (TheraBand) set at 40-50% of 1RM.
Resistance Training Exercises:
Control Group:
Participants received general guidance on physical activity benefits and were given Mi Smart Band 4 for activity monitoring.
Weekly phone calls were conducted to encourage increased step counts. Step counts were recorded during the first and eighth weeks for comparison.
Measurements and Assessments
Oxygen Consumption:
Measured using Cardiopulmonary Exercise Testing (CPET) on a treadmill (COSMED, Quark RMR) with the Modified Bruce Protocol. Peak VO2 and anaerobic thresholds were recorded, along with parameters such as ventilatory efficiency, heart rate, and metabolic equivalents.
Muscle Oxygenation:
Measured during CPET using near-infrared spectroscopy (NIRS) (Moxy, Fortiori Design LLC). Parameters included SmO2 and total hemoglobin changes (THb).
Peripheral Muscle Strength:
Assessed using a digital hand dynamometer (LaFayette Instrument Company) and isometric contractions. Strength of various muscle groups (e.g., quadriceps, hamstrings, shoulder abductors) was evaluated using standardized positions.
Respiratory Muscle Strength:
Maximal inspiratory (MIP) and expiratory pressures (MEP) were measured using a portable mouth pressure device (Micro RPM). Results were recorded in cmH2O and compared to age- and gender-specific predicted values.
Body Composition:
Measured using Bioelectrical Impedance Analysis (BIA) (Bodystat QuadScan 4000). Parameters included body fat percentage, lean mass, and phase angle. Skinfold measurements were performed using a caliper, and quadriceps muscle thickness and cross-sectional area were evaluated using ultrasound.
Frailty:
Evaluated using the Liver Frailty Index (LFI), which includes grip strength, sit-to-stand time, and balance tests. Scores classified participants as robust, pre-frail, or frail.
Physical Activity Levels:
Assessed using the International Physical Activity Questionnaire-Short Form (IPAQ). Scores were calculated in MET-min/week and classified as inactive, minimally active, or sufficiently active.
Fatigue:
Measured using the Fatigue Severity Scale (FSS), with responses recorded via an online form before and after the intervention.
Quality of Life:
Evaluated using the Chronic Liver Disease Questionnaire (CLDQ), addressing abdominal symptoms, fatigue, systemic symptoms, activity, emotional functioning, and anxiety.
Health-Related Lifestyle Behaviors:
Assessed using the Health-Promoting Lifestyle Profile II (HPLP-II), covering six domains: spiritual growth, interpersonal relations, nutrition, physical activity, health responsibility, and stress management.
Statistical Analysis Data were analyzed using descriptive and inferential statistics. Continuous variables were expressed as mean ± SD or median (min-max), while categorical variables were summarized as frequencies and percentages.
Dependent group comparisons: Paired t-tests or Wilcoxon Signed Rank tests were applied.
Independent group comparisons: ANOVA or Kruskal-Wallis tests, followed by post hoc tests (Tukey HSD or Mann-Whitney U).
A p-value <0.05 was considered statistically significant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (%). |
| Measure | Description | Time Frame |
|---|---|---|
| Physical Activity Level (IPAQ) | Physical activity levels were assessed using the International Physical Activity Questionnaire-Short Form (IPAQ), validated in Turkish. The questionnaire includes seven items evaluating time spent sitting, walking, and performing moderate and vigorous physical activities over the past seven days. Activities performed for at least 10 continuous minutes were considered. MET-min/week scores were calculated by multiplying activity duration (minutes), frequency (days), and MET values (walking: 3.3 MET, moderate: 4.0 MET, vigorous: 8.0 MET). Total physical activity was classified as inactive, minimally active, or sufficiently active based on IPAQ scoring. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Naciye Vardar Yağlı, Prof | Hacettepe University Faculty of Physical Therapy and Rehabilitation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hacettepe University Faculty of Physical Therapy and Rehabilitation | Ankara | Altındağ | 06100 | Turkey (Türkiye) |
Individual participant data (IPD) underlying the results reported in any publication will be shared upon reasonable request. Data are securely stored at Hacettepe University and will be made available to researchers who provide a methodologically sound proposal, following applicable regulations and ethical guidelines. Access to data will be granted only for research purposes that align with the goals of this study.
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.
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.
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|
| 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. |
|
| 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. |
| Baseline and at 8 weeks. |
| Quality of Life (Chronic Liver Disease Questionnaire - CLDQ) | Quality of life was assessed using the Chronic Liver Disease Questionnaire (CLDQ), validated in Turkish. The CLDQ comprises six subdomains (abdominal symptoms, fatigue, systemic symptoms, activity, emotional function, and worry) and a total of 29 items. Each item is rated on a 7-point Likert scale, ranging from 1 ("always") to 7 ("never"). Higher total scores indicate better quality of life. Participants were asked to evaluate issues experienced in the past two weeks. The questionnaire was administered via an online platform (Google Forms) before and after the intervention. | Baseline and at 8 weeks. |
| Health-Promoting Lifestyle Behaviors (HPLP-II) | Health-promoting lifestyle behaviors were assessed using the Health-Promoting Lifestyle Profile II (HPLP-II), validated in Turkish. The HPLP-II evaluates health-related behaviors across six subdomains: spiritual growth, interpersonal relations, nutrition, physical activity, health responsibility, and stress management. The scale consists of 52 items rated on a 4-point Likert scale (1 = "never," 2 = "sometimes," 3 = "often," 4 = "always"), with higher scores indicating better health-promoting behaviors. The questionnaire was administered online via Google Forms before and after the intervention. | Baseline and at 8 weeks. |
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D058625 | End Stage Liver Disease |
| D009043 | Motor Activity |
| D055948 | Sarcopenia |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001519 | Behavior |
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D044382 | Population Groups |
| ID | Term |
|---|---|
| D003710 | Demography |
| D011154 | Population Characteristics |
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