Frailty in Patients With Cirrhosis: Prognostic Value of the Phase Angle in Hospitalized Patients and Effect of Multifactorial Intervention

Frailty in Patients With Cirrhosis: Prognostic Value of the Phase Angle in Hospitalized Patients and Effect of a Multifactorial Intervention (Home Exercise, Branched-chain Aminoacids and Probiotic)

This study evaluate Frailty syndrome (FS) as a common syndrome in patients with cirrhosis and it is an independent predictor of hospitalizations, falls and mortality. Identifying, treating and preventing FS can improve the prognosis and quality of life of these patients and reduce health costs.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Frailty Syndrome; Cirrhosis of the Liver
• Intervention / Treatment: Combination product: Home exercise program for 12 months.; Combination product: Multispecies probiotic: Vivomixx®; Combination product: Branched-chain amino acids (BCAA); Combination product: No specific intervention.

Detailed Description

Substudy I. The phase angle (PA) determined by electrical bioimpedance is an index of FS with prognostic value in outpatients with cirrhosis, but its usefulness in hospitalized patients has not been studied. Objective: To analyze the prognostic value of PA in hospitalized patients with cirrhosis. Patients and Methods: 100 hospitalized patients with cirrhosis will be consecutively included and PA will be determined by bioimpedance at admission. The correlation between PA and liver function and frailty markers, and the evolution during hospitalization, as well as the incidence of falls, hospitalizations and mortality during follow-up will be analyzed. Substudy II. Given the multidimensional nature of the FS, we propose a multifactorial non-pharmacological intervention based on evidence from previous studies that could be implemented in daily clinical practice. Objective: To evaluate if a multifactorial intervention can improve the FS and decrease the related events (hospitalizations, falls and mortality) in patients with cirrhosis. Patients and Methods: 150 outpatients with cirrhosis will be included and evaluated using the Liver Frailty Index. Frail and pre-frail patients will be randomized into two groups: one group that will receive a multifactorial intervention, consisting of exercise at home, branched-chain amino acids and multispecies probiotic for one year, and one control group. The evolution of the Liver Frailty Index and other parameters (muscle and cognitive function, bioimpedance, risk of falls, quality of life) and biomarkers (miostatin, immune response, microbiota) of FS, and the incidence of hospitalizations, falls and mortality in both groups will be prospectively analyzed.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients
• Aged >18 years old, with cirrhosis diagnosed by clinical, analytical and ultrasound criteria or liver biopsy
• Conscious and oriented in time and space and able to understand and follow the indications of the study.

Exclusion Criteria:

• Liver cirrhosis with poor prognosis (MELD [Model for End Stage Liver Disease]> 25)
• Hepatocellular carcinoma or other active neoplastic disease
• Expected survival <6 months
• Acute and/or chronic hepatic encephalopathy
• Neurological disorder that hinders the performance of the tests
• Active alcoholism in the previous 3 months
• Severe comorbidities
• Hospitalization in the previous month
• Contraindications to exercise or probiotic treatment (immunosuppression)
• Refusal to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multifactorial intervention; Frail and pre-frail patients will receive multifactorial intervention consisting of home exercise, BCAA supplements and a multispecies probiotic for 12 months.	Combination product: Home exercise program for 12 months.; Physical exercise at home: At the beginning of the study, group sessions will be conducted with 5 patients of 1-hour duration, where they will be taught the individualized program according to their physical condition and they will be given the necessary material (pedaling, dumbbells and elastic bands) and paper support on the program, also using the Vivifrail method through infographics. The group session will be repeated every 3 months to check the compliance of the program by reviewing daily activity, evaluate possible problems and review the exercises. The program will consist of aerobic and anaerobic exercise by pedaling (cardiovascular resistance) and resistance exercises with dumbbells and elastic bands (muscular strength), flexibility training by stretching, and coordination and balance exercises. Patients will perform 3 sessions per week of 20-30 min. increasing progressively according to tolerance up to 45-60 min. each.; Combination product: Multispecies probiotic: Vivomixx®; Multispecies probiotic: Vivomixx® is a probiotic mixture of 8 bacterial strains: Streptococcus thermophilus DSM 24731® / NCIMB 30438, Bifidobacterium breve DSM 24732® / NCIMB 30441, Bifidobacterium longum DSM 24736® / NCIMB 30435*, Bifidobacterium infantis DSM 24737® / NCIMB 30436*, Lactobacillus acidophilus DSM 24735® / NCIMB 30442, Lactobacillus plantarum DSM 24730® / NCIMB 30437, Lactobacillus paracasei DSM 24733® / NCIMB 30439, Lactobacillus delbrueckii subsp. bulgaricus DSM 24734® / NCIMB 30440** * Re-classified as B. lactis ** Re-classified as L. helveticus The active agent will be supplied as an envelope of 4.4 g with a dose of 450x109 million live bacteria per envelope with maltose and silicon dioxide as excipients, administered 2 times/day throughout the study.; Combination product: Branched-chain amino acids (BCAA); Branched-chain amino acids (BCAA): In addition to the exercise program and the probiotic, patients in the intervention group will receive BCAA supplements (powder in 8:1:1 ratio in favor of L-leucine) 10 g 30-60 min. before the exercise session throughout the study, in order to enhance the effect of exercise on muscle mass and improve cognitive function. We have chosen this dose based on the literature data and the satisfactory results obtained with this dose in our previous study. BCAA supplements will be supplied by the Pharmacy Service of our center.
Experimental: Control group; Frail and pre-frail patients will be followed but will not receive any specific intervention.	Combination product: No specific intervention.; Follow up as a clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substudy I: Mortality during hospitalization and follow-up	At the time of admission, during hospitalization and in one hundred outpatients visits every 3 months until 12 months of follow-up	One year
Substudy II: Evolution of the Liver Frailty Index.	At the beginning and every 3 months in one hundred fifty outpatient visits until the end of the study at 12 months	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase angle (PA)	By bioimpedance (BIA 101 with Bodygram Pro software, Akern) at admission, hospital discharge and every 3 months.	One year
Degree of sarcopenia	Grip strength assessed by a dynamometer (KERN MAP 80K1, Akern). The results will be adjusted by age and gender	One year
Biomarkers of frailty	At baseline and at 12 months.We will quantify by specific ELISA kits and multiplex assays biomarkers	One year
Fall risk tests	Walking speed (41) and Timed Up & Go: time in seconds that the patient uses to get up from a chair, walk 3 meters and sit back without support. Times greater than 9 seconds to travel the distance is considered a risk of falls	One year
Cognitive function	Psychometric Hepatic Encephalopathy Score (PHES). Scores <-4 points is considered as a cognitiva impairment	One year
Fecal microbiota	At baseline, 6 and 12 months.For the extraction of genomic DNA from stool samples, a previous protocol according to the International consortium (IHMS: http://www.microbiome-standards.org/) will be used.	One year
Degree Quality of life	Depression and anxiety scale (HADS): Scores higher than 11 are probably cases in each of the subscales	One year
Degree of Quality of life	SF-36 questionnaire - Scores above 50 will be better and below 50 points will be worse.	One year

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Investigators: Principal Investigator: Germán Soriano, PhD, Hospital Sant Pau

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: January 14, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Body Composition; Mortality; Falls; Hospitalizations; Phase angle
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Liver Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Fibrosis; Liver Cirrhosis; Frailty; Sarcopenia
• Other Study ID Numbers: IIBSP-FRA-2019-36

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
• product manufactured in and exported from the U.S.: No