Role of Exercise in Chronic Liver Disease Patients Undergoing Liver Transplantation

Frailty Clinical Trial

Official title:

Effects of Supervised Aerobic and Resistance Exercises on Measures of Frailty in Chronic Liver Disease Patients Undergoing Living Donor Liver Transplantation- an Open Label Randomised Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06163001
• Other study ID #: ILBS-LDLT-02
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 15, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: August 2023
• Source: Institute of Liver and Biliary Sciences, India
• Contact: Sambhav Gupta
• Phone: 01146300000
• Email: drsambhavgupta[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this randomised clinical trial (open label) is to test the effect of supervised aerobic and resistance exercises in chronic liver disease patients being planned for living donor liver transplantation (LDLT). The main question it aims to answer are:

• If pre-operative supervised aerobic and resistance exercise for 4 weeks can improve the measures of frailty (Liver frailty index, Short physical performance battery, pulmonary function tests) in chronic liver disease patients being planned for LDLT.

• Can this approach also translate into clinically significant benefits in the postoperative outcomes of LDLT.

Participants will be randomised into two groups receiving either

1. Standard medical therapy along with supervised aerobic and resistance exercises for 4 weeks.

2. Standard medical therapy. The two groups will be compared for progression of the measures of frailty ver the course of their participation as well as their post LDLT outcomes.

Description:

1. Aim and Objective - Primary objective: To assess effects of pre-operative aerobic and resistance exercises in decompensated CLD patients planned for LDLT on the measures of frailty after 1 month of supervised exercise.

Secondary objectives: To assess effects of pre-operative aerobic and resistance exercises in decompensated CLD patients planned for LDLT on the post LDLT outcomes, myostatin levels (on POD 14) and skeletal muscle mass (on POD14).

2. Methodology:

• Study population - Consecutive voluntary adults (>18 years) with chronic liver disease, planned for living donor liver transplantation fulfilling the conditions as per inclusion and exclusion criteria.

• Study design - Interventional study- Open label randomised controlled trial

• Study period - From time of ethical clearance till 31st December 2024

• Sample size - Assuming median LFI for CLD patients as 3.9 ± 0.3*, and assuming an improvement of 5% with introduction of exercise along with SMT after 1 follow up, and keeping alpha of 5%, and power of study as 90%, with 1:1 ratio of cases and controls, then by method of change we need to enroll a total of 54 patients with 27 in each arm. Assuming 10% non compliance, a total of 60 cases will be enrolled, with 30 cases in each arm.

• Intervention - Pre-operative supervised exercise-based regimen versus standard medical therapy alone for a minimum duration of 4 weeks.

• Monitoring and assessment - Clinical profile of the patient and symptoms will be serially followed during the patients OPD visits.

• Adverse effects - Exercise may aggravate encephalopathy, metabolic disorders, AKI/HRS. It may also lead to falls due to cardio-pulmonary intolerance or hepatic encephalopathy.

• Stopping rule - Inability to follow the exercise schedule, or development of any of the adverse effects due to exercise as mentioned above.

3. Expected outcome of the project: Better values of measures of frailty and post LDLT outcomes in patients receiving pre-operative concurrent exerises as an intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 30, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Voluntary adult patient (>18 years), decompensated chronic liver disease patients planned for LDLT, and Who pass the screening tests done in the OPD

1. Able to follow the introductory level exercises as per the protocol in the OPD without any adverse event.

2. No drop in the spO2 less than 93% on a 6 minute walk test.

Exclusion Criteria:

1. Patients with a physical disability (upper or lower limb deformity/abnormality)

2. Exercise intolerance or inability to follow exercise regime.

3. Patients who fail the screening tests.

4. Patients on the following drugs-

• Higher corticosteroid dose (>0.1mg/kg/day),

• BCAA (Branched chain amino acids)

• Growth hormone, testosterone, SARMs,

• Ghrelin agonists, myostatin antibodies,

• Activin IIR antagonists, angiotensin converting enzyme inhibitors,

• Espindolol (mixed beta agonist and antagonists), and

• Fast skeletal muscle troponin activators.

Related Conditions & MeSH terms

• Chronic Liver Disease and Cirrhosis
• Frailty
• Liver Diseases

Intervention

Behavioral:
• Supervised aerobic and resistance exercises
4 weeks of preoperative supervised aerobic and resistance exercises

Dietary Supplement:
• Dietary supplementation
4 weeks of preoperative Standard medical therapy which will consist of dietary advice and supplementation

Locations

Country	Name	City	State
India	Institute of Liver and Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Liver frailty index	Robust defined as LFI <3.2, prefrail defined as LFI between 3.2 and 4.4, and frail defined as LFI =4.5	4 weeks post intervention, Post op day 14, Post op day 30
Primary	short physical performance battery	SPPB scores range from zero to 12 possible points. SPPB score of 3-9 points in persons with possible sarcopenia but no mobility disability indicates frailty; SPPB score of 10 or greater for persons with no sarcopenia and no mobility disability indicates robustness	4 weeks post intervention, Post op day 14, Post op day 30
Primary	pulmonary function test	PEF would be tested	4 weeks post intervention, Post op day 14, Post op day 30
Primary	pulmonary function test	FEV1 would be tested	4 weeks post intervention, Post op day 14, Post op day 30
Secondary	Time to extubation		Till Post op day 90
Secondary	Need for re-intubation		Till Post op day 90
Secondary	Duration of NIV support		Till Post op day 90
Secondary	Mortality		90 days
Secondary	Myostatin levels in blood		Post intervention at 4 weeks & on Post op day 14
Secondary	Skeletal muscle mass- L3 Skeletal Muscle Index		Post intervention at 4 weeks & on Post op day 14
Secondary	Time to mobilization out of bed		Till Post op day 90
Secondary	Length (Days) of ICU stay		Till Post op day 90
Secondary	Number of days of hospital stay		Till Post op day 90
Secondary	Incidence of all septic complications		Till Post op day 90
Secondary	Major surgical complications (CDC > grade 3)		Till Post op day 90
Secondary	Pulmonary complications- Clinical evaluation		Till Post op day 90