Nutrition and Exercise Prehabilitation in Patients Awaiting Liver Transplantation (POWER-LT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplantation; Liver Cirrhosis; Malnutrition; Frailty; Sarcopenia; End-stage Liver Disease
• Intervention / Treatment: Behavioral: Diet with even protein distribution plus exercise program; Behavioral: Diet with skewed protein distribution plus exercise program; Behavioral: Standard dietary and physical activity advice

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kalliopi Anna Poulia; Phone Number: +30 2105294668; Email: lpoulia@aua.gr
• Study Contact Backup: Name: Evangelos Cholongitas; Phone Number: +30 2132061643; Email: echolog@med.uoa.gr

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11855
      • Recruiting
      • Agricultural University of Athens
      • Contact: Kalliopi Anna Poulia; Phone Number: +30 2105294668; Email: lpoulia@aua.gr
    • Athens, Attica, Greece, 11527
      • Recruiting
      • Laiko General Hospital of Athens
      • Contact: Evangelos Cholongitas; Phone Number: +30 2132061643; Email: echolog@med.uoa.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet with even protein distribution plus exercise program	Behavioral: Diet with even protein distribution plus exercise program; 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
Experimental: Diet with skewed protein distribution plus exercise program	Behavioral: Diet with skewed protein distribution plus exercise program; 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
Active Comparator: Standard dietary and physical activity advice	Behavioral: Standard dietary and physical activity advice; Standard dietary and physical activity advice | Duration: 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition	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.	Baseline, 12 weeks
Changes in Computed Tomography (CT)-derived muscle mass	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.	Baseline, 12 weeks
Changes in handgrip strength (kg)	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.	Baseline, 12 weeks
Changes in Short Physical Performance Battery (SPPB) score	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.	Baseline, 12 weeks
Changes in Liver Frailty Index	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.	Baseline, 12 weeks
Changes in European Working Group on Sarcopenia in Older People 2 (EWGSOP2)-derived sarcopenia	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.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional Risk Screening-2002 (NRS-2002)-derived nutritional risk	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.	Baseline
Malnutrition Screening Tool (MST)-derived nutritional risk	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.	Baseline
Malnutrition Universal Screening Tool (MUST)-derived nutritional risk	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.	Baseline
Short Nutritional Assessment Questionnaire (SNAQ)-derived nutritional risk	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.	Baseline
Mini Nutritional Assessment-Short Form (MNA-SF)-derived nutritional status	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.	Baseline
Nutritional Risk Index (NRI)-derived nutritional risk	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.	Baseline
Prognostic Nutritional Index (PNI)-derived nutritional status	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.	Baseline
Controlling Nutritional Status (CONUT)-derived nutritional status	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.	Baseline
Liver Disease Undernutrition Screening Tool (LDUST)-derived nutritional risk	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.	Baseline
Royal Free Hospital-Nutritional Prioritizing Tool (RHT-NPT)-derived nutritional status	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.	Baseline
Dual-Energy X-ray Absorptiometry (DEXA)-derived muscle mass	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.	Baseline
Food Frequency Questionnaire (FFQ)-derived dietary habits	Long-term dietary habits will be assessed using a semi-quantitative Food Frequency Questionnaire (FFQ).	Baseline
International Physical Activity Questionnaire (IPAQ)-derived physical activity levels	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.	Baseline
Changes in Bioelectrical Impedance Analysis (BIA)-derived muscle mass	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.	Baseline, 12 weeks
Changes in body weight (kg)	Body weight (kg) will be measured using a calibrated weight scale.	Baseline, 12 weeks
Changes in Body Mass Index (BMI, kg/m^2)	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.	Baseline, 12 weeks
Changes in Mid-Arm Muscle Circumference (MAMC, cm)	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.	Baseline, 12 weeks
Changes in Bristol Stool Chart	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	Baseline, 12 weeks
Changes in Chronic Liver Disease Questionnaire (CLDQ)	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.	Baseline, 12 weeks
Changes in aspartate aminotransferase (AST, U/L)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in alanine aminotransferase (ALT, U/L)	Data will be collected through medical chart review	Baseline, 12 weeks
Changes in alkaline phosphatase (ALP, U/L)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in gamma-glutamyltransferase (GGT, U/L)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in total bilirubin (mg/dL)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in direct bilirubin (mg/dL)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in International Normalized Ratio (INR)	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in MELD-Na score	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%)	Baseline, 12 weeks
Changes in Child-Pugh score	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]	Baseline, 12 weeks
Changes in presence of oedema and/or ascites	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in presence of jaundice	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in presence of variceal bleeding	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in presence of infections	Data will be collected through medical chart review.	Baseline, 12 weeks
Changes in presence of hepatic encephalopathy	Data will be collected through medical chart review.	Baseline, 12 weeks
Mortality	Data will be collected through medical chart review.	From baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to the program	Adherence to the program will be assessed using 24-hour recalls and physical activity diaries.	4 weeks, 8 weeks, 12 weeks
Satisfaction with the program	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	12 weeks
Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition	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	3 months post-transplantation
Computed Tomography (CT)-derived muscle mass	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 months post-transplantation
Handgrip strength (kg)	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.	3 months post-transplantation
Short Physical Performance Battery (SPPB) score	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.	3 months post-transplantation
Liver Frailty Index	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.	3 months post-transplantation
European Working Group on Sarcopenia in Older People 2 (EWGSOP2)-derived sarcopenia	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	3 months post-transplantation
Body weight (kg)	Body weight (kg) will be measured using a calibrated weight scale.	3 months post-transplantation
Body Mass Index (BMI, kg, m^2)	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.	3 months post-transplantation
Mid-Arm Muscle Circumference (MAMC, cm)	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.	3 months post-transplantation
Bristol Stool Chart	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	3 months post-transplantation
Chronic Liver Disease Questionnaire (CLDQ)	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.	3 months post-transplantation
Aspartate aminotransferase (AST, U/L)	Data will be collected through medical chart review.	3 months post-transplantation
Alanine aminotransferase (ALT, U/L)	Data will be collected through medical chart review.	3 months post-transplantation
Alkaline phosphatase (ALP, U/L)	Data will be collected through medical chart review.	3 months post-transplantation
Gamma-glutamyltransferase (GGT, U/L)	Data will be collected through medical chart review.	3 months post-transplantation
Total bilirubin (mg/dL)	Data will be collected through medical chart review.	3 months post-transplantation
Direct bilirubin (mg/dL)	Data will be collected through medical chart review.	3 months post-transplantation
International Normalized Ratio (INR)	Data will be collected through medical chart review.	3 months post-transplantation
Length of hospital stay	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Length of intensive care unit stay	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Duration of mechanical ventilation	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Postoperative complications	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Hospital readmissions	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Reoperations	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation
Mortality	Data will be collected through medical chart review.	From transplantation to 3 months post-transplantation

Collaborators and Investigators

• Sponsor: Kalliopi Anna Poulia
• Collaborators: Laikο General Hospital, Athens

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: exercise; quality of life; frailty; nutritional status; nutrition; liver transplantation; physical performance; body composition; sarcopenia; prehabilitation; malnutrition; end-stage liver disease; diet; functional status; liver cirrhosis; protein; liver disease; nutrition therapy; protein distribution
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathologic Processes; Nutrition Disorders; Pathological Conditions, Anatomical; Digestive System Diseases; Muscular Atrophy; Atrophy; Liver Failure; Hepatic Insufficiency; Fibrosis; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Frailty; Malnutrition; Liver Diseases; Liver Cirrhosis; Sarcopenia; End Stage Liver Disease; Motor Activity; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet
• Other Study ID Numbers: 113/05.12.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No