Comparison of the Effect of Two Interventions on Liver Frailty Index in Pre-frail and Frail Cirrhotic Patients Enlisted for Liver Transplantation

NCT06149026 | Unknown DMC

• 1 other identifier: FrailtyRCT
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective, double blind randomized clinical trial is to compare the effectiveness of two interventions in improve frailty (measured by Liver Frailty Index) and quality of life (measured by Chronic Liver Disease Questionnaire - CLDQ) in listed patients with cirrhosis. The main questions it aims to answer are:

• if the intervention group (physical and nutritional therapy) could improve LFI over control group (physical and nutritional counseling).
• if the intervention group could improve secondary outcomes as CLDQ, hand grip and gait velocity. Participants will be evaluated in a registry of basal variables such as demographic factors, weight, height and brachial circumference, comorbidities, MELD and MELD-Na, Child Pugh classification, general blood exams, etiology of cirrhosis, presence of hepatocellular carcinoma, ascites, or hepatic encephalopathy and their basal LFI, gait velocity, hand grip and CLDQ. The participants will be randomized in an intervention group or in a control group at the same time of their first evaluation and will receive the group instructions depending on what group the participants belong, and will be evaluated at 4 weeks, 8 weeks, and 12 weeks with applying LFI, measuring of gait velocity, hand grip and a nutritional survey with the intake in the last 24 hours. Finally, researchers will compare interventional group with control group if the first group could improve frailty, measured by Liver Frailty Index and the secondary outcomes with the nutritional and physical therapy.

Conditions

Cirrhosis, Liver

Keywords

liver transplant; cirrhosis; nutrition; physical therapy; frailty; quality of life

Outcome Measures

Primary Outcomes (1)

• Liver Frailty Index

  The Liver Frailty Index (LFI) is a test developed to be used specifically in patients with cirrhosis, evaluates objective variables, requires simple instruments, is reproducible, widely available and requires few time to be performed. In addition, it predicts the survival of listed patients.

  12 weeks

Secondary Outcomes (3)

• Chronic Liver Disease Questionnaire

  12 weeks

• Gait velocity

  12 weeks

• Hand grip

  12 weeks

Study Arms (2)

Control group

NO INTERVENTION

The control group will receive written, detailed, and standardized instructions on nutritional recommendations and physical activity at visit 1. Patients will have follow-up evaluations by a physician to reinforce adherence and make necessary adjustments for compliance with nutritional requirements. Nutritional intake reminder surveys will be conducted during the last 24 hours (E24H) at weeks 0, 4, 8 and 12.

Intervention group

EXPERIMENTAL

Intervention group consisting of physical therapy guided by a kinesiologist for 10 sessions during which the patient will be trained to maintain physical activity three times a week. In addition, patients will be evaluated by a nutritionist who will give specific indications regarding the quality, quantity, and timing of food intake, as well as the daily frequency of food consumption. Patients will have two follow-ups by a nutritionist (week 4 and 8) to check adherence and make the necessary adjustments to meet nutritional requirements. Nutritional intake reminder surveys will be conducted during the last 24 hours (E24H) at weeks 0, 4, 8 and 12.)

Other: Physical and nutritional therapy

Interventions

Physical and nutritional therapy OTHER

The patients will be evaluated and followed by a nutritionist and a physical therapist for 12 weeks. In that time, the patients will receive workouts according to their evaluations and a specific nutritional guide according to the nutritionist's evaluations.

Intervention group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of cirrhosis.
• Over 50 years old.
• Liver Frailty Index of 3.2 points or more.
• Ability to follow instructions.
• Ability to consent to study entry.

You may not qualify if:

• Grade 3 or 4 hepatic encephalopathy.
• Untreated HIV infection.
• Previous liver transplant.
• Inability to walk.
• Extrahepatic diseases that limit mobility (e.g., neurological or musculoskeletal).
• Advanced cardiac, renal or pulmonary disease.
• Expectation of being transplanted during the study period.
• Hepatocarcinoma (HCC) exceeding the Milan criteria.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, Chile

RECRUITING

Related Publications (19)

• Tandon P, Montano-Loza AJ, Lai JC, Dasarathy S, Merli M. Sarcopenia and frailty in decompensated cirrhosis. J Hepatol. 2021 Jul;75 Suppl 1(Suppl 1):S147-S162. doi: 10.1016/j.jhep.2021.01.025.

  PMID: 34039486 BACKGROUND

• Puchades Renau L, Herreras Lopez J, Cebria I Iranzo MA, Cezon Serrano N, Di Maira T, Berenguer M. Frailty and Sarcopenia in Acute-on-Chronic Liver Failure. Hepatol Commun. 2021 May 4;5(8):1333-1347. doi: 10.1002/hep4.1722. eCollection 2021 Aug.

  PMID: 34430779 BACKGROUND

• Laube R, Wang H, Park L, Heyman JK, Vidot H, Majumdar A, Strasser SI, McCaughan GW, Liu K. Frailty in advanced liver disease. Liver Int. 2018 Dec;38(12):2117-2128. doi: 10.1111/liv.13917. Epub 2018 Jul 15.

  PMID: 29935102 BACKGROUND

• Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, Dunn MA; Fitness, Life Enhancement, and Exercise in Liver Transplantation Consortium. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl. 2017 May;23(5):625-633. doi: 10.1002/lt.24750.

  PMID: 28240805 BACKGROUND

• Lai JC, Sonnenday CJ, Tapper EB, Duarte-Rojo A, Dunn MA, Bernal W, Carey EJ, Dasarathy S, Kamath BM, Kappus MR, Montano-Loza AJ, Nagai S, Tandon P. Frailty in liver transplantation: An expert opinion statement from the American Society of Transplantation Liver and Intestinal Community of Practice. Am J Transplant. 2019 Jul;19(7):1896-1906. doi: 10.1111/ajt.15392. Epub 2019 May 8.

  PMID: 30980701 BACKGROUND

• Ney M, Haykowsky MJ, Vandermeer B, Shah A, Ow M, Tandon P. Systematic review: pre- and post-operative prognostic value of cardiopulmonary exercise testing in liver transplant candidates. Aliment Pharmacol Ther. 2016 Oct;44(8):796-806. doi: 10.1111/apt.13771. Epub 2016 Aug 19.

  PMID: 27539029 BACKGROUND

• Soto R, Diaz LA, Rivas V, Fuentes-Lopez E, Zalaquett M, Bruera MJ, Gonzalez C, Mezzano G, Benitez C. Frailty and reduced gait speed are independently related to mortality of cirrhotic patients in long-term follow-up. Ann Hepatol. 2021 Nov-Dec;25:100327. doi: 10.1016/j.aohep.2021.100327. Epub 2021 Feb 14.

  PMID: 33596465 BACKGROUND

• Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, Feng S. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017 Aug;66(2):564-574. doi: 10.1002/hep.29219. Epub 2017 Jun 28.

  PMID: 28422306 BACKGROUND

• Williams FR, Berzigotti A, Lord JM, Lai JC, Armstrong MJ. Review article: impact of exercise on physical frailty in patients with chronic liver disease. Aliment Pharmacol Ther. 2019 Nov;50(9):988-1000. doi: 10.1111/apt.15491. Epub 2019 Sep 9.

  PMID: 31502264 BACKGROUND

• Haugen CE, McAdams-DeMarco M, Verna EC, Rahimi RS, Kappus MR, Dunn MA, Volk ML, Gurakar A, Duarte-Rojo A, Ganger DR, O'Leary JG, Ladner D, Garonzik-Wang J, Segev DL, Lai JC. Association Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index. JAMA Surg. 2019 Dec 1;154(12):1103-1109. doi: 10.1001/jamasurg.2019.2845.

  PMID: 31509169 BACKGROUND

• Lai JC, Dodge JL, Kappus MR, Wong R, Mohamad Y, Segev DL, McAdams-DeMarco M. A Multicenter Pilot Randomized Clinical Trial of a Home-Based Exercise Program for Patients With Cirrhosis: The Strength Training Intervention (STRIVE). Am J Gastroenterol. 2021 Apr;116(4):717-722. doi: 10.14309/ajg.0000000000001113.

  PMID: 33982941 BACKGROUND

• Hughes MJ, Hackney RJ, Lamb PJ, Wigmore SJ, Christopher Deans DA, Skipworth RJE. Prehabilitation Before Major Abdominal Surgery: A Systematic Review and Meta-analysis. World J Surg. 2019 Jul;43(7):1661-1668. doi: 10.1007/s00268-019-04950-y.

  PMID: 30788536 BACKGROUND

• Zenith L, Meena N, Ramadi A, Yavari M, Harvey A, Carbonneau M, Ma M, Abraldes JG, Paterson I, Haykowsky MJ, Tandon P. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014 Nov;12(11):1920-6.e2. doi: 10.1016/j.cgh.2014.04.016. Epub 2014 Apr 24.

  PMID: 24768811 BACKGROUND

• Williams FR, Vallance A, Faulkner T, Towey J, Durman S, Kyte D, Elsharkawy AM, Perera T, Holt A, Ferguson J, Lord JM, Armstrong MJ. Home-Based Exercise in Patients Awaiting Liver Transplantation: A Feasibility Study. Liver Transpl. 2019 Jul;25(7):995-1006. doi: 10.1002/lt.25442. Epub 2019 Jun 6.

  PMID: 30859755 BACKGROUND

• Chen HW, Ferrando A, White MG, Dennis RA, Xie J, Pauly M, Park S, Bartter T, Dunn MA, Ruiz-Margain A, Kim WR, Duarte-Rojo A. Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial. Dig Dis Sci. 2020 Nov;65(11):3350-3359. doi: 10.1007/s10620-019-06034-2. Epub 2020 Jan 6.

  PMID: 31907774 BACKGROUND

• Ng TP, Feng L, Nyunt MS, Feng L, Niti M, Tan BY, Chan G, Khoo SA, Chan SM, Yap P, Yap KB. Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial. Am J Med. 2015 Nov;128(11):1225-1236.e1. doi: 10.1016/j.amjmed.2015.06.017. Epub 2015 Jul 6.

  PMID: 26159634 BACKGROUND

• Roman E, Garcia-Galceran C, Torrades T, Herrera S, Marin A, Donate M, Alvarado-Tapias E, Malouf J, Nacher L, Serra-Grima R, Guarner C, Cordoba J, Soriano G. Effects of an Exercise Programme on Functional Capacity, Body Composition and Risk of Falls in Patients with Cirrhosis: A Randomized Clinical Trial. PLoS One. 2016 Mar 24;11(3):e0151652. doi: 10.1371/journal.pone.0151652. eCollection 2016.

  PMID: 27011355 BACKGROUND

• Kruger C, McNeely ML, Bailey RJ, Yavari M, Abraldes JG, Carbonneau M, Newnham K, DenHeyer V, Ma M, Thompson R, Paterson I, Haykowsky MJ, Tandon P. Home Exercise Training Improves Exercise Capacity in Cirrhosis Patients: Role of Exercise Adherence. Sci Rep. 2018 Jan 8;8(1):99. doi: 10.1038/s41598-017-18320-y.

  PMID: 29311671 BACKGROUND

• Lattanzi B, Bruni A, Di Cola S, Molfino A, De Santis A, Muscaritoli M, Merli M. The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study. Nutrients. 2021 Jul 2;13(7):2296. doi: 10.3390/nu13072296.

  PMID: 34371806 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis; Frailty

Interventions

Restraint, Physical; Nutrition Therapy

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques

Central Study Contacts

Diego Reyes, Dr.

CONTACT

+56974686699; diegoreyesplacencia@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A person who do not participate in the recruitment and the evaluation of the patients randomize a number for each patient. If the number is even, the patient belongs to the intervention group and if the number is odd, the patient belongs to the control group.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellowship of gastroenterology

Model Details: The goal of this prospective, double blind randomized clinical trial is to compare the effectiveness of two interventions in improve frailty (measured by Liver Frailty Index) and quality of life (measured by Chronic Liver Disease Questionnaire - CLDQ) in listed patients with cirrhosis.

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: November 28, 2023
• Study Start: February 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The data will become available when the study will be published in a journal in a supplementary material.
• Access Criteria: The access will be defined by the journal.

Locations

CL (1)