A Home-based Exercise and Physical Activity Intervention After Liver Transplantation: Impact of Exercise Intensity (PHOENIX-L)

A Home-based Exercise and Physical Activity Intervention After Liver Transplantation: Impact of Exercise Intensity - a Monocenter Randomized Controlled Trial [PHOENIX-Liver]

Research demonstrated that transplant recipients benefit from physical activity, but there is a gap in knowledge regarding the required intensity. In the PHOENIX-Liver study, researchers aim to investigate the adequate intensity of rehabilitation programs after liver transplantation. Patients will be randomized into one of the three PHOENIX-Liver training groups (low, moderate, moderate to high). The six months rehabilitation program is conducted from the patient's home but supervised by a PHOENIX-investigator.

At baseline, after three months of rehabilitation and after six months of rehabilitation, a test moment takes place at which physical fitness, cardiovascular health, liver function, and body composition will be assessed. Questionnaires are taken monthly to survey well-being, safety, quality of life, physical activity, and cost-effectiveness.

To gather information on the potential for implementation in a real-world setting, a 15-month-long physical activity phase will start after the intervention phase. This entails a maintenance physical activity program tailored to the patients' preferences. A follow-up at UZ Leuven is planned at three and at 15 months where the same clinical evaluations will be conducted as during the test moments of the intervention phase.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplantation; Physical Fitness
• Intervention / Treatment: Other: Physical activity; Other: Sham intervention

Detailed Description

Liver transplantation constitutes the only curative treatment for patients with end-stage liver disease. Advances in the field have led to favourable short- and medium term (1-3 year) post-transplant survival rates, but improvement in long-term survival rates remains disappointing. Due to the immunosuppressive therapy, a sedentary lifestyle and a poor recovery of post-transplant physical fitness, the proportion of liver transplant recipients that develop a new-onset or a deteriorating unfavourable cardiovascular risk profile is alarmingly high, and cardiovascular disease is the leading cause of death in this population. By consequence, in order to improve long-term outcome after liver transplantation, prevention of cardiovascular disease should be prioritized. The investigators are convinced that the challenge of cardiovascular disease and lack of physical fitness in liver transplant recipients should and can be addressed by subjecting these patients to a structured physical rehabilitation program. The aim of this project is implement a structured, individually-tailored, home-based but supervised physical rehabilitation and maintenance program for de novo liver transplantation recipients, and to demonstrate the feasibility and safety of such approach as well as its efficacy to improve physical fitness. The program will consist of a 2-phase intervention of i) home-based exercise training (aerobic exercise training as well as strength, flexibility and stability exercises under in-person and subsequently remote guidance) and ii) an 15-month maintenance phase of physical activity. This program will be studied in an open-label randomized trial where the regimen will be compared with a regimen of standard of posttransplant care. In addition to the interventional arm, two different regimens of exercise training intensity will also be studied.

• Study Type: Interventional
• Enrollment (Estimated): 147
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Diethard Monbaliu, MD PhD; Phone Number: +3216342361; Email: diethard.monbaliu@uzleuven.be
• Study Contact Backup: Name: Stefan De Smet, PhD; Email: stefan.desmet@kuleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven
      • Principal Investigator: Diethard Monbaliu, MD PhD
      • Contact: Hanne Van Criekinge; Phone Number: +3216343162; Email: hanne.vancriekinge@kuleuven.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• de novo adult liver transplant recipients with a transplant vintage of two to three months
• access to a home freezer (± -18°C)

Exclusion Criteria:

• Aberrant CPET (abnormal low cardiorespiratory fitness is not considered an exclusion criteria), unstable angina, life-threatening arrhythmias, uncontrolled hypertension/diabetes, HbA1c ≥ 9%, severe pulmonary disease (FEV1 < 50%), musculoskeletal disorders not allowing physical training on a cycle ergometer, or any other medical reasons by the physician considered to be a contraindication for moderate or high-intensity physical exercise
• multi-organ transplantation (exception: combined liver-kidney transplant is considered eligible for participation)
• ongoing treatment for malignancies
• unable to understand Dutch
• no access to smartphone and/or computer with internet access
• does not willing to except the general conditions of Coachbox. Preparticipation medical screening (cardiopulmonary exercise testing with 12-lead ECG + stratification of cardiovascular risk factors) will be performed by a cardiologist (Dr. Kaatje Goetschalckx at UZ Leuven).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Group; Home-based low-intensity exercise training without subsequent physical activity intervention.	Other: Sham intervention; 2 times a week, flexibility and balance training
Experimental: Moderate-intensity (MIT); Home-based moderate-intensity exercise training with subsequent physical activity intervention.	Other: Physical activity; The home-based training intervention consists of two phases of each three months in duration. It consists of three weekly aerobic training sessions on the one hand, and two weekly training sessions focused on strength, balance, and flexibility on the other hand.
Experimental: Combined moderate and high-intensity (MHIT); Home-based moderate- and high-intensity exercise training with subsequent physical activity intervention.	Other: Physical activity; The home-based training intervention consists of two phases of each three months in duration. It consists of three weekly aerobic training sessions on the one hand, and two weekly training sessions focused on strength, balance, and flexibility on the other hand.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory fitness	Changes in peak oxygen uptake (mL O2·min-1·kg-1) assessed by cardiopulmonary exercise test	At 0, 3 and 6 months of the interventional rehabilitation programme and at 15 months after the end of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional exercise capacitiy	six-minute walking test (m)	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Hand grip strength	assessement by means of Jamar Hydraulic Hand Dynamometry (kg)	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Knee-extensor strength	assessement by means of Biodex dynamometer (Nm)	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Endothelial function	assessed via flow mediated dilation	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Arterial stiffness	assessed via pulse wave velocity	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Graft function	Transient elastography Fibroscan assessing liver stiffness	At 0 and after 21 months
Occurence of adverse events	Safety is estimated by means of questionnaires	Monthly
Motor fitness	Short Physical Performance Battery test	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Blood pressure	Variation in blood pressure measured by means of automatic device (Omron M6) in fasted condition and without medication taken in	At 0, 3 and 6 months of the interventional rehabilitation programme and 15 months after the end of the intervention
Blood profile	Blood is drawn when patient is in fasted condition and did not take their medication	At 0, 3 and 6 months of the interventional rehabilitation programme, and at 3 and 15 months after the end of the intervention

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Exercise Intensity
• Other Study ID Numbers: S66232

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