Frailty in Liver Transplant Exercise (FLEX) Trial

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Frailty in Liver Transplant Exercise (FLEX) Trial

Conditions
-----------------
Frailty, Liver Transplants

Intervention / Treatment
-----------------
* Behavioral: Exercise intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An interventional pilot trial will be performed with 21 randomized subjects who are aged 18-75 years who are frail according to the LFI to a 3-month exercise intervention (n=14) versus standard of care (n=7) with no change in activity.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise intervention<br>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<br>* 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.<br>|
| No Intervention: Control<br>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 |