ACCESS-ESLD: Relevance of Sarcopenia in Advanced Liver Disease

Sponsor

Linkoeping University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05502198

Collaborator

Amra Medical AB (Industry)

100

Enrollment

Location

112.9

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with established liver cirrhosis, or end-stage liver disease (ESLD), are at high risk of developing liver cancer (hepatic carcinoma; HCC), portal hypertension, and sarcopenia, all which lead to significant morbidity and mortality. In this patient group the annual incidence of HCC is c. 2-8% and these patients are therefore included in ultrasound HCC screening programs every 6 months.

In this study, the investigators are aiming to assess sarcopenia, clinically significant portal hypertension (CSPH), and HCC with a single short magnetic resonance (MR) examination. A neck-to-knee MRI-examination will be acquired to derive body composition profile (BCP) measurements including visceral and abdominal subcutaneous adipose tissue (VAT and ASAT), thigh fat free muscle volume (FFMV) and muscle fat infiltration (MFI), as well as liver fat (PDFF), spleen volume, and liver stiffness. Images will be further processed by AMRA Medical AB. AMRA's solution includes FFMV in the context of virtual control groups (VCG; using AMRA's vast database) and MFI. Furthermore, the spleen volume will be used to monitor the development of portal hypertension and explored together with other BCP variables in relation to hepatic decompensation events. HCC screening will be performed using so-called abbreviated MRI (AMRI), which consists of time series of contrast-enhanced T1-weighted images. The AMRI images will be read by an experienced radiologist. In the literature the sensitivity of AMRI to detect HCC is above 80%, with a specificity of c. 95%, compared to ultrasound sensitivity of 60%.

In treating ESLD there is a desire of physicians to be able to predict future decompensation events in order to initiate treatment to prolong survival. Moreover, the ability to assess processes of sarcopenia in the patient would be highly valuable for clinical practice due its severe clinical impact. Finally, ultrasound-based HCC screening has poor diagnostic performance and a MR-based screening approach would significantly improve treatment outcome as more treatable and earlier HCC may be identified.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis Hepatocellular Carcinoma Sarcopenia Portal Hypertension

Detailed Description

100 patients with established or probable liver cirrhosis at the Department of Gastroenterology and Hepatology at Linköping University Hospital will be included in the study. The study includes four visits every six months; each patient participates actively in the study during a time period of approximately 24 months. All study visits are scheduled in conjunction with clinical routine visits.

During each study visit the following is performed:

A detailed clinical work-up
Assessment of medical history or changes in health status since last visit
FibroScan
Magnetic resonance (MR) examination
Comprehensive blood panels and blood samples for research
Muscle function and mobility assessments (SPPB and hand grip strength).
Quality of life assessment (EQ-5D-5L, QLDQ-cirrhosis and SHS-liver).
Hepatic encephalopathy assessment (ANT test).
Assessment of the development of symptoms

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Rapid, Non-invasive, Clinical Surveillance for CachExia, Sarcopenia, Portal Hypertension and Hepatocellular Carcinoma in End-Stage Liver Disease

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2030

Outcome Measures

Primary Outcome Measures

Body composition (FFMVvcg) [Baseline]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Body composition (FFMVvcg) [6 months]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Body composition (FFMVvcg) [1 year]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Body composition (FFMVvcg) [18 months]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Change from baseline Body composition (FFMVvcg) [6 months]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Change from 6 months Body composition (FFMVvcg) [1 year]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Change from 1 year Body composition (FFMVvcg) [18 months]
FFMVvcg is the thigh fat-free muscle volume in the context of virtual controls which effectively measures the deviation from expected thigh fat-free muscle volume normalized to height squared using sex and BMI matched virtual control groups.
Muscle fat infiltration (%) [MFI] [Baseline]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Muscle fat infiltration (%) [MFI] [6 months]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Muscle fat infiltration (%) [MFI] [1 year]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Muscle fat infiltration (%) [MFI] [18 months]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Change from baseline Muscle fat infiltration (%) [MFI] [6 months]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Change from 6 months Muscle fat infiltration (%) [MFI] [1 year]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Change from 1 year Muscle fat infiltration (%) [MFI] [18 months]
MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
Presence of previous decompensation [Baseline]
If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since baseline [6 months]
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since 6 months [1 year]
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since 1 year [18 months]
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
New episode of decompensation since 18 months [2 years]
If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
Hepatocellular carcinoma [Baseline]
Detection of HCC by AMRI
Hepatocellular carcinoma [6 months]
Detection of HCC by AMRI
Hepatocellular carcinoma [1 year]
Detection of HCC by AMRI
Hepatocellular carcinoma [18 months]
Detection of HCC by AMRI
Hepatocellular carcinoma [2 years]
Chart review
Hand grip strength (kg) [Baseline]
Measured at each visit with a hand-grip dynamometer
Hand grip strength (kg) [6 months]
Measured at each visit with a hand-grip dynamometer
Hand grip strength (kg) [1 year]
Measured at each visit with a hand-grip dynamometer
Hand grip strength (kg) [18 months]
Measured at each visit with a hand-grip dynamometer
Muscle function [Baseline]
Measured using the validated Short Physical Performance Battery.
Muscle function [6 months]
Measured using the validated Short Physical Performance Battery.
Muscle function [1 year]
Measured using the validated Short Physical Performance Battery.
Muscle function [18 months]
Measured using the validated Short Physical Performance Battery.
Child-Pugh score [Baseline]
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
Child-Pugh score [6 months]
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
Child-Pugh score [1 year]
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
Child-Pugh score [18 months]
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
Child-Pugh score [2 year]
A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
MELD-score [Baseline]
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
MELD-score [6 months]
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
MELD-score [1 year]
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
MELD-score [18 months]
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
MELD-score [2 years]
A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

Secondary Outcome Measures

Death [6 months]
Chart review
Death [1 year]
Chart review
Death [18 months]
Chart review
Death [2 years]
Chart review
Esophageal varices [Baseline]
Assessed by gastroscopy and captured through chart review.
Development of Esophageal varices [6 months]
Assessed by gastroscopy and captured through chart review.
Development of Esophageal varices [1year]
Assessed by gastroscopy and captured through chart review.
Development of Esophageal varices [18 months]
Assessed by gastroscopy and captured through chart review.
Development of Esophageal varices [2 years]
Assessed by gastroscopy and captured through chart review.
Liver stiffness by Fibroscan (kPa) [Baseline]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by Fibroscan (kPa) [6 months]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by Fibroscan (kPa) [1 year]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by Fibroscan (kPa) [18 months]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by MRE (kPa) [Baseline]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by MRE (kPa) [6 months]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by MRE (kPa) [1 year]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Liver stiffness by MRE (kPa) [18 months]
Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
Spleen volume (ml) [Baseline]
A surrogate marker for portal hypertension and measured by MR.
Spleen volume (ml) [6 months]
A surrogate marker for portal hypertension and measured by MR.
Spleen volume (ml) [1 year]
A surrogate marker for portal hypertension and measured by MR.
Spleen volume (ml) [18 months]
A surrogate marker for portal hypertension and measured by MR.
Quality of life (Questionnaire) [Baseline]
EQ-5D-5L
Quality of life (Questionnaire) [6 months]
EQ-5D-5L
Quality of life (Questionnaire) [1 year]
EQ-5D-5L
Quality of life (Questionnaire) [18 months]
EQ-5D-5L
Quality of life (Questionnaire) [Baseline]
Short Health Scale-liver
Quality of life (Questionnaire) [6 months]
Short Health Scale-liver
Quality of life (Questionnaire) [1 year]
Short Health Scale-liver
Quality of life (Questionnaire) [18 months]
Short Health Scale-liver

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Established or probable liver cirrhosis according to clinical practice at the Department of Gastroenterology and Hepatology at Linköping University Hospital. This is not by necessity biopsy verified, it can be different criteria such as FibroScan, symptoms, biopsy, and radiology.
Age ≥18 years
Written informed consent from the participant