Frailty in Liver Transplant Exercise (FLEX) Trial (FLEX)

Frailty is common in patients with end-stage liver disease. It's characterized by reduced strength, low endurance and reduced physical function. While exercise intervention can improve frailty in geriatric patients without liver disease, whether or not exercise intervention can improve frailty in liver transplant candidates remains unknown.

Study Overview

• Status: Withdrawn
• Conditions: Frailty; Liver Transplants
• Intervention / Treatment: Behavioral: Exercise intervention

Detailed Description

The long-term goal is to better understand how exercise impacts frailty in order to identify treatments that can improve both patient-oriented outcomes and access to liver transplantation for end-stage liver disease patients. The specific objective of this proposal is to generate pilot feasibility data required for future multicenter R01 application to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) which will test the novel central hypothesis that exercise improves frailty and lessens waiting-list mortality. Additionally, another goal of the study is to establish an optimal frailty tool for liver transplant candidates.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults age ≥18 or ≤75 years
• Frail as defined by a LFI score of >4.5
• Under evaluation or listed for liver transplant

Exclusion Criteria:

• Active cardiac symptoms (e.g., chest pain, shortness of breath at rest, palpitations)
• Positive response to Get Active Questionnaire (GAQ) (validated activity questionnaire that indicates if exercise is unsafe)
• Institutionalized/prisoner
• Severe medical comorbidities/psychiatric illness at the discretion of the Study Principal Investigator (PI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Exercise intervention; Private supervised strength training exercise (e.g., body weight or dumbbell exercises) will occur in the Cancer Center Exercise Medicine Unit or the Hershey Center for Applied Research (HCAR) two days a week. In addition, subjects will be instructed to exercise on their own, at home, three days a week doing 30 minutes of moderate intensity aerobic exercise (e.g., walking at 45-55% maximum heart rate determined by the formula max heart rate = 220bpm - 0.64*age in years).	Behavioral: Exercise intervention; Subjects in this group will be asked to exercise 5 days a week. Two days on-site with an Exercise Physiologist and the other 3 days at home.
NO_INTERVENTION: Control; Subjects in the control condition will be instructed to continue their medical care at the discretion of their treating medical professional and to maintain their current exercise level. Weekly phone calls will be performed to ensure adherence to the protocol (no changes in activity). Subjects will report to Penn State on a monthly basis for interim history and physical to confirm self-reports. Subjects will also be given a FitBit ChargeHR3 and downloaded data review will be performed monthly at the in-person visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants able to complete the trial	Defined as 50% of subjects completing >80% of the sessions.	up to 52 weeks
Incidence of Treatment-Emergent Adverse Events as assessed by GCP guidelines	This study aims to examine the incidence of adverse events. If exercise in frail liver transplant candidates is safe. 5% serious adverse events or fewer will deem the trial as safe. If more than 5% serious adverse events occur, the trial is determined to be unsafe.	up to 52 weeks
Rate of enrollment	Net enrollment rates, which are calculated by dividing the number of subjects approached by the number of subjects that enroll in the trial. The work with the ongoing NASHFit and completed ENACT Trials and the work of others performing exercise-based trials in patients with cirrhosis(50) has established >50% enrollment of subjects approached as a threshold of acceptability.	up to 52 weeks

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2021
• Primary Completion (ANTICIPATED): February 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (ACTUAL): December 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 25, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: STUDY00014084

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