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NCT Number: NCT07561138

Nutrition and Exercise Prehabilitation in Patients Awaiting Liver Transplantation

This study aims to evaluate the effects of a diet with even protein distribution plus exercise (Group A) versus a diet with skewed protein distribution plus exercise (Group B) versus standard dietary and physical activity advice (Group C) on nutritional status, body composition and functional status in patients awaiting liver transplantation.

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Key information

Conditions

End-Stage Liver DIsease Atrophy Behavior Digestive System Diseases End Stage Liver Disease Fibrosis Frailty Hepatic Insufficiency Liver Cirrhosis Liver Diseases Liver Failure Liver Transplantation Malnutrition Motor Activity Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Nutrition Disorders Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Sarcopenia Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Agricultural University of Athens, Athens, Attica, Greece

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About this study

Malnutrition and sarcopenia affect many patients awaiting liver transplantation and is associated with reduced quality of life and increased mortality. According to the current European Society for Clinical Nutrition and Metabolism (ESPEN) and European Association for the Study of the Liver (EASL) guidelines, a target of 1.2-1.5 g protein per kg body weight daily is recommended for patients with decompensated liver cirrhosis. While evidence supports that even protein distribution enhances muscle protein synthesis in healthy adults, specific protein timing recommendations are lacking for patients with end-stage liver disease.

Therefore, this randomized controlled trial aims to investigate the effects of a 12-week diet with even protein distribution plus exercise (Group A) versus skewed protein distribution plus exercise (Group B) versus standard dietary and physical activity advice (Group C), primarily on nutritional status, body composition and functional status, and secondarily on anthropometric measurements, laboratory parameters, quality of life, disease severity, complications and mortality in liver transplant candidates. Moreover, late postoperative parameters, including length of hospital stay, length of intensive care unit stay, duration of mechanical ventilation, postoperative complications, hospital readmissions, reoperations and mortality will be examined for those who undergo transplantation.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • End-stage liver disease, diagnosed by transient elastography (FibroScan) or imaging-based evaluation with compatible clinical picture
  • Referred for liver transplantation and evaluated to have a high likelihood of being listed, according to primary hepatologist assessment, or already listed for liver transplantation
  • No prior formal dietary advice

Exclusion criteria

  • Age < 18 years old
  • Estimated waiting time for liver transplantation < 3 months
  • Estimated life expectancy < 3 months
  • Chronic kidney disease requiring protein restriction
  • Exercise contraindicated (e.g., active or recent variceal bleeding, severe grade of hepatic encephalopathy, refractory ascites, etc.)
  • Unstable or severe psychiatric disorder
  • Pregnancy or lactation
  • Inability to provide written informed consent

Treatment and study plan

Diet with even protein distribution plus exercise program

Behavioral

Diet of 1.2-1.5 g protein/kg dry body weight/day, equally divided (33.3% at 3 main meals) | Exercise program: 3 days/week aerobic and 2 days/week resistance | Duration: 12 weeks

Diet with skewed protein distribution plus exercise program

Behavioral

Diet of 1.2-1.5 g protein/kg dry body weight/day, unequally divided (10.0% at breakfast, 60.0% at lunch, 30.0% at dinner) | Exercise program: 3 days/week aerobic and 2 days/week resistance | Duration: 12 weeks

Standard dietary and physical activity advice

Behavioral

Standard dietary and physical activity advice | Duration: 12 weeks

Primary outcomes

  1. Changes in Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition

    Time frame: Baseline, 12 weeks

    Malnutrition will be diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Diagnosis requires at least 1 phenotypic criterion and 1 etiologic criterion. Phenotypic criteria include: a. Non-votional weight loss (%): > 5% within past 6 months or > 10% beyond 6 months, b. Low body mass index (BMI, kg/m^2): < 20 kg/m^2 if < 70 years or < 22 kg/m^2 if > 70 years, c. Reduced muscle mass, assessed by validated body composition measuring techniques [e.g. Dual-Energy X-ray Absorptiometry (DEXA), Bioelectrical Impedance Analysis (BIA) or Computed Tomography (CT)]. Etiologic criteria include: a. Reduced food intake or assimillation: ≤ 50% of energy requirements > 1 week or any reduction for > 2 weeks or any chronic gastrointestinal condition that adversely impacts food assimilation or absorption, b. Inflammation: acute disease/injury or chronic disease-related.

  2. Changes in Computed Tomography (CT)-derived muscle mass

    Time frame: Baseline, 12 weeks

    Muscle mass will be assessed using the Skeletal Muscle Index (SMI, cm^2/m^2). SMI will be calculated by measuring the total cross-sectional area of skeletal muscles, from a single cross-sectional Computed Tomography (CT) image at L3 vertebral level, using Hounsfield Units of -29 to +150 HU, and normalizing to height squared (m^2).Thresholds for reduced SMI will be considered < 50 cm^2/m^2 for men and < 39 cm^2/m^2 for women.

  3. Changes in handgrip strength (kg)

    Time frame: Baseline, 12 weeks

    Handgrip strength (kg) will be assessed using a digital handgrip dynamometer. Thresholds for reduced muscle strength will be considered < 27 kg for men and < 16 kg for women.

  4. Changes in Short Physical Performance Battery (SPPB) score

    Time frame: Baseline, 12 weeks

    The Short Physical Performance Battery (SPPB) includes 3 components: 3-positions balance testing (sec) (0-4 points), 4-meter gait speed test (sec) (0-4 points) and 5-times chair stand test (sec) (0-4 points), with a total score of 0-12. Higher scores indicate a better physical performance: 0-3 points for worst physical performance, 4-9 points for reduced physical performance and 10-12 points for best physical performance.

  5. Changes in Liver Frailty Index

    Time frame: Baseline, 12 weeks

    The Liver Frailty Index includes 3 components: handgrip strength (kg), 5-times chair stand test (sec) and 3-positions balance testing (sec). Higher scores indicate a greater degree of frailty.

  6. Changes in European Working Group on Sarcopenia in Older People 2 (EWGSOP2)-derived sarcopenia

    Time frame: Baseline, 12 weeks

    Sarcopenia will be diagnosed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Diagnosis requires low muscle strength and low muscle mass. Reduced muscle strength will be diagnozed by: a. Low handgrip strength (kg): > 27 kg for men and > 16 kg for women or b. Low chair stand test (sec): >15 sec for 5-times chair stand test. Reduced muscle mass will be diagnozed by: a. Low Appendicular Skeletal Muscle Mass (ASM, kg): < 20 kg for men and < 15 kg for women or b. Low Appendicular Skeletal Muscle Mass Index (ASMI, kg/m^2): <7.0 kg/m^2 for men and < 5.5 kg/m^2 for women.

Secondary outcomes

  1. Nutritional Risk Screening-2002 (NRS-2002)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Nutritional Risk Screening-2002 (NRS-2002) tool. Higher scores indicate greater nutritional risk: < 3 points indicate good nutritional status and ≥ 3 nutritional risk.

  2. Malnutrition Screening Tool (MST)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Malnutrition Screening Tool (MST) tool. Higher scores indicate greater nutritional risk: < 2 points indicate good nutritional status and ≥ 2 nutritional risk.

  3. Malnutrition Universal Screening Tool (MUST)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Malnutrition Universal Screening Tool (MUST) tool. Higher scores indicate greater nutritional risk: 0 points indicate low risk, 1 point medium risk and ≥ 2 high risk.

  4. Short Nutritional Assessment Questionnaire (SNAQ)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Short Nutritional Assessment Questionnaire (SNAQ) tool. Higher scores indicate greater nutritional risk: 0-1 points indicate low risk, 2 points medium risk and ≥ 3 points high risk.

  5. Mini Nutritional Assessment-Short Form (MNA-SF)-derived nutritional status

    Time frame: Baseline

    Nutritional risk will be assessed using the Mini Nutritional Assessment-Short Form (MNA-SF) tool. Lower scores indicate greater nutritional risk: 12-14 points indicate good nutritional status, 8-11 points risk of malnutrition and 0-7 points malnutrition.

  6. Nutritional Risk Index (NRI)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Nutritional Risk Index (NRI) tool. Lower scores indicate greater nutritional risk: > 100.0 indicate good nutritional status, 97.5-100.0 low risk, 83.5-97.5 medium risk and < 83.5 high risk.

  7. Prognostic Nutritional Index (PNI)-derived nutritional status

    Time frame: Baseline

    Nutritional risk will be assessed using the Prognostic Nutritional Index (PNI) tool. Lower scores indicate greater nutritional risk: ≥ 50 indicate good nutritional status, < 50 low risk, < 45 medium risk and < 40 high risk.

  8. Controlling Nutritional Status (CONUT)-derived nutritional status

    Time frame: Baseline

    Nutritional risk will be assessed using the Controlling Nutritional Status (CONUT) tool. Higher scores indicate greater nutritional risk: 0-1 points indicate good nutritional status, 2-4 points low risk, 5-8 medium risk and 9-12 high risk.

  9. Liver Disease Undernutrition Screening Tool (LDUST)-derived nutritional risk

    Time frame: Baseline

    Nutritional risk will be assessed using the Liver Disease Undernutrition Screening Tool (LDUST) tool. ≥ 5 answers "A" indicate good nutritional status and ≥ 2 answers "B" and/or "C" malnutrition.

  10. Royal Free Hospital-Nutritional Prioritizing Tool (RHT-NPT)-derived nutritional status

    Time frame: Baseline

    Nutritional risk will be assessed using the Royal Free Hospital-Nutritional Prioritizing Tool (RHT-NPT) tool. Higher scores indicate greater nutritional risk: 0 points indicate low risk, 1 point medium risk and 2-7 points high risk.

  11. Dual-Energy X-ray Absorptiometry (DEXA)-derived muscle mass

    Time frame: Baseline

    Muscle mass will be assessed using the Appendicular Skeletal Muscle Mass Index (ASMI, kg/m^2) using Dual-Energy X-ray Absorptiometry (DEXA). Thresholds for reduced muscle mass will be considered < 7.0 for men and < 5.4 for women.

  12. Food Frequency Questionnaire (FFQ)-derived dietary habits

    Time frame: Baseline

    Long-term dietary habits will be assessed using a semi-quantitative Food Frequency Questionnaire (FFQ).

  13. International Physical Activity Questionnaire (IPAQ)-derived physical activity levels

    Time frame: Baseline

    Physical activity levels will be assessed using the International Physical Activity Questionnaire (IPAQ)-Short Form. IPAQ includes 7 open-ended questions. Higher scores (MET-min/week) indicate higher physical activity levels.

  14. Changes in Bioelectrical Impedance Analysis (BIA)-derived muscle mass

    Time frame: Baseline, 12 weeks

    Muscle mass will be assessed using the Appendicular Skeletal Muscle Mass Index (ASMI, kg/m^2) by Bioelectrical Impedance Analysis (BIA). Thresholds for reduced ASMI will be considered < 7.0 for men and < 5.7 for women.

  15. Changes in body weight (kg)

    Time frame: Baseline, 12 weeks

    Body weight (kg) will be measured using a calibrated weight scale.

  16. Changes in Body Mass Index (BMI, kg/m^2)

    Time frame: Baseline, 12 weeks

    Body Mass Index (BMI, kg, m^2) will be calculated by dividing body weight (kg) by height squared (m^2), which will be measured using a calibrated stadiometer.

  17. Changes in Mid-Arm Muscle Circumference (MAMC, cm)

    Time frame: Baseline, 12 weeks

    Mid-Arm Muscle Circumference (MAMC, cm) will be calculated using the following formula: MAMC (cm) = Mid-Arm Circumference (MAC, cm) - [0.314*Triceps Skinfold Thickness (TSF, mm)]. MAC will be measured using a non-stretchable measuring tape and TSF using a calibrated skinfold caliper. Thresholds for reduced MAMC will be considered < 25 cm for men and < 22 cm for women.

  18. Changes in Bristol Stool Chart

    Time frame: Baseline, 12 weeks

    Bowel habits will be assessed using the Bristol Stool Chart. Bristol Stool Chart classifies stool forms in 7 types: types 1-2 indicate constipation, types 3-4 normal stool form, and types 5-7 looser stools tending toward diarrhea

  19. Changes in Chronic Liver Disease Questionnaire (CLDQ)

    Time frame: Baseline, 12 weeks

    Quality of life will be assessed using the Chronic Liver Disease Questionnaire (CLDQ). CLDQ includes 29 items in 6 domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. Each is scored on a 7-point scale, with higher domain and total scores indicating a better quality of life.

  20. Changes in aspartate aminotransferase (AST, U/L)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  21. Changes in alanine aminotransferase (ALT, U/L)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review

  22. Changes in alkaline phosphatase (ALP, U/L)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  23. Changes in gamma-glutamyltransferase (GGT, U/L)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  24. Changes in total bilirubin (mg/dL)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  25. Changes in direct bilirubin (mg/dL)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  26. Changes in International Normalized Ratio (INR)

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  27. Changes in MELD-Na score

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review. Higher MELD-Na scores indicate greater severity of chronic liver disease and higher predictive risk of mortality (< 17 points: <2%, 17-20 points: 3-4%, 21-22 points: 7-10%, 23-26 points: 14-15%, 27-31 points: 27-32%, ≥ 32 points: 65-66%)

  28. Changes in Child-Pugh score

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review. Higher Child-Pugh scores indicate greater severity of liver cirrhosis [class A (5-6 points): mild, class B: (7-9 points): moderate, class C (10-15) points: severe]

  29. Changes in presence of oedema and/or ascites

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  30. Changes in presence of jaundice

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  31. Changes in presence of variceal bleeding

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  32. Changes in presence of infections

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  33. Changes in presence of hepatic encephalopathy

    Time frame: Baseline, 12 weeks

    Data will be collected through medical chart review.

  34. Mortality

    Time frame: From baseline to 12 weeks

    Data will be collected through medical chart review.

Other outcomes

  1. Adherence to the program

    Time frame: 4 weeks, 8 weeks, 12 weeks

    Adherence to the program will be assessed using 24-hour recalls and physical activity diaries.

  2. Satisfaction with the program

    Time frame: 12 weeks

    Satisfaction with the program will be assessed using a Likert scale: very satisfied, fairly satisfied, neither satisfied nor dissatisfied, slightly dissatisfied and not at all satisfied

  3. Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition

    Time frame: 3 months post-transplantation

    Malnutrition will be diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Diagnosis requires at least 1 phenotypic criterion and 1 etiologic criterion. Phenotypic criteria: a. Non-votional weight loss (%): > 5% within past 6 months or >10% beyond 6 months b. Low body mass index (BMI, kg/m^2): < 20 kg/m^2 if < 70 years or < 22 kg/m^2 if > 70 years c. Reduced muscle mass, assesses by validated body composition measuring techniques [e.g. Dual-Energy X-ray Absorptiometry (DEXA), Bioelectrical Impedance Analysis (BIA) or Computed Tomography (CT) Etiologic criteria: a. Reduced food intake or assimillation: ≤ 50% of energy requirements > 1 week or any reduction for > 2 weeks or any chronic gastrointestinal condition that adversely impacts food assimilation or absorption b. Inflammation: acute disease/injury or chronic disease-related

  4. Computed Tomography (CT)-derived muscle mass

    Time frame: 3 months post-transplantation

    Muscle mass will be assessed using the Skeletal Muscle Index (SMI, cm^2/m^2). SMI will be calculated by measuring the total cross-sectional area of skeletal muscles, from a single cross-sectional Computed Tomography (CT) image at L3 vertebral level, using Hounsfield Units of -29 to +150 HU, and normalizing to height squared (m^2).Thresholds for reduced SMI will be considered < 50 cm^2/m^2 for men and < 39 cm^2/m^2 for women.

  5. Handgrip strength (kg)

    Time frame: 3 months post-transplantation

    Handgrip strength (kg) will be assessed using a digital handgrip dynamometer. Thresholds for reduced muscle strength will be considered < 27 kg for men and < 16 kg for women.

  6. Short Physical Performance Battery (SPPB) score

    Time frame: 3 months post-transplantation

    The Short Physical Performance Battery (SPPB) includes 3 components: 3-positions balance testing (sec) (0-4 points), 4-meter gait speed test (sec) (0-4 points) and 5-times chair stand test (sec) (0-4 points), with a total score of 0-12. Higher scores indicate a better physical performance: 0-3 points for worst physical performance, 4-9 points for reduced physical performance and 10-12 points for best physical performance.

  7. Liver Frailty Index

    Time frame: 3 months post-transplantation

    The Liver Frailty Index includes 3 components: handgrip strength (kg), 5-times chair stand test (sec) and 3-positions balance testing (sec). Higher scores indicate a greater degree of frailty.

  8. European Working Group on Sarcopenia in Older People 2 (EWGSOP2)-derived sarcopenia

    Time frame: 3 months post-transplantation

    Sarcopenia will be diagnosed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) diagnostic criteria. Diagnosis requires the presence of low muscle strength and low muscle mass. Reduced muscle strength: a. Low handgrip strength (kg): > 27 kg for men and > 16 kg for women b. Low chair stand test (sec): >15 sec for 5 rises Reduced muscle mass: a. Low Appendicular Skeletal Muscle Mass (ASM, kg): < 20 kg for men and < 15 kg for women b. Low Appendicular Skeletal Muscle Mass Index (ASMI, kg/m^2): <7.0 kg/m^2 for men and < 5.5 kg/m^2 for women

  9. Body weight (kg)

    Time frame: 3 months post-transplantation

    Body weight (kg) will be measured using a calibrated weight scale.

  10. Body Mass Index (BMI, kg, m^2)

    Time frame: 3 months post-transplantation

    Body Mass Index (BMI, kg, m^2) will be calculated by dividing body weight (kg) by height squared (m^2), which will be measured using a calibrated stadiometer.

  11. Mid-Arm Muscle Circumference (MAMC, cm)

    Time frame: 3 months post-transplantation

    Mid-Arm Muscle Circumference (MAMC, cm) will be calculated using the following formula: MAMC (cm) = Mid-Arm Circumference (MAC, cm) - [0.314*Triceps Skinfold Thickness (TSF, mm)]. MAC will be measured using a non-stretchable measuring tape and TSF using a calibrated skinfold caliper. Thresholds for reduced MAMC will be considered < 25 cm for men and < 22 cm for women.

  12. Bristol Stool Chart

    Time frame: 3 months post-transplantation

    Bowel habits will be assessed using the Bristol Stool Chart. Bristol Stool Chart classifies stool forms in 7 types: types 1-2 indicate constipation, types 3-4 normal stool form, and types 5-7 looser stools tending toward diarrhea

  13. Chronic Liver Disease Questionnaire (CLDQ)

    Time frame: 3 months post-transplantation

    Quality of life will be assessed using the Chronic Liver Disease Questionnaire (CLDQ). CLDQ includes 29 items in 6 domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. Each is scored on a 7-point scale, with higher domain and total scores indicating a better quality of life.

  14. Aspartate aminotransferase (AST, U/L)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  15. Alanine aminotransferase (ALT, U/L)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  16. Alkaline phosphatase (ALP, U/L)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  17. Gamma-glutamyltransferase (GGT, U/L)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  18. Total bilirubin (mg/dL)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  19. Direct bilirubin (mg/dL)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  20. International Normalized Ratio (INR)

    Time frame: 3 months post-transplantation

    Data will be collected through medical chart review.

  21. Length of hospital stay

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  22. Length of intensive care unit stay

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  23. Duration of mechanical ventilation

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  24. Postoperative complications

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  25. Hospital readmissions

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  26. Reoperations

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

  27. Mortality

    Time frame: From transplantation to 3 months post-transplantation

    Data will be collected through medical chart review.

Study contacts

Contact information is provided by the study sponsor or research team.

Evangelos Cholongitas

CONTACT

[email protected]

+30 2132061643

Kalliopi Anna Poulia

CONTACT

[email protected]

+30 2105294668

Sponsors and collaborators

Lead sponsor

Kalliopi Anna Poulia

Other

Collaborators

  • Laikο General Hospital, Athens

Registry information

Official study title

Evaluation of Protein Distribution Optimization With Exercise Regimen on Nutritional Status, Body Composition and Functional Status in Patients Awaiting Liver Transplantation: The POWER-LT Randomized Clinical Trial

Acronym: POWER-LT

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
May 1, 2026
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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