Relevance of Sarcopenia in Advanced Liver Disease

Hepatocellular Carcinoma Clinical Trial

— ACCESS-ESLD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05502198
• Other study ID #: 2020-07215
• Status: Recruiting
• Start date: February 1, 2021
• Est. completion date: June 30, 2030

Study information

• Verified date: August 2023
• Source: Linkoeping University
• Contact: Mattias Ekstedt, MD, PhD
• Phone: +46709296267
• Email: mattias.ekstedt[@]liu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

150 patients with established or probable liver cirrhosis at the Department of Gastroenterology and Hepatology at Linköping University Hospital, as well as collaborating hospitals; District Hospital in Eksjö and County Hospital in Jönköping, will be included in the study. The study includes four visits every six months (in patients with LI-RADS 3 five visits will be performed); 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 30, 2030
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Age =18 years

3. Written informed consent from the participant

Exclusion Criteria:

1. Contraindications for MRI

2. Subjects suffering from primary sclerosing cholangitis (PSC)

3. Subjects diagnosed with Hepatic carcinoma (HCC)

4. Previous liver transplant

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Liver Diseases
• Portal Hypertension
• Sarcopenia

Locations

Country	Name	City	State
Sweden	Department of Gastroenterology), District Hospital in Eksjö	Eksjö
Sweden	Department of gastroenterology, County Hospital in Jönköping	Jönköping
Sweden	Department of gastroenterology and hepatology	Linköping

Sponsors (2)

Lead Sponsor	Collaborator
Linkoeping University	Amra Medical AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body composition (FFMVvcg)	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.	Baseline
Primary	Body composition (FFMVvcg)	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.	6 months
Primary	Body composition (FFMVvcg)	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.	1 year
Primary	Body composition (FFMVvcg)	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.	18 months
Primary	Change from baseline Body composition (FFMVvcg)	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.	6 months
Primary	Change from 6 months Body composition (FFMVvcg)	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.	1 year
Primary	Change from 1 year Body composition (FFMVvcg)	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.	18 months
Primary	Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	Baseline
Primary	Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	6 months
Primary	Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	1 year
Primary	Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	18 months
Primary	Change from baseline Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	6 months
Primary	Change from 6 months Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	1 year
Primary	Change from 1 year Muscle fat infiltration (%) [MFI]	MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).	18 months
Primary	Presence of previous decompensation	If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.	Baseline
Primary	New episode of decompensation since baseline	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	6 months
Primary	New episode of decompensation since 6 months	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	1 year
Primary	New episode of decompensation since 1 year	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	18 months
Primary	New episode of decompensation since 18 months	If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.	2 years
Primary	Hepatocellular carcinoma	Detection of HCC by AMRI	Baseline
Primary	Significant liver lesion	LI-RADS 3-5	Baseline
Primary	Significant liver lesion	LI-RADS 3-5	6 months
Primary	Significant liver lesion	LI-RADS 3-5	1 year
Primary	Significant liver lesion	LI-RADS 3-5	18 months
Primary	Hepatocellular carcinoma	Detection of HCC by AMRI	6 months
Primary	Hepatocellular carcinoma	Detection of HCC by AMRI	1 year
Primary	Hepatocellular carcinoma	Detection of HCC by AMRI	18 months
Primary	Hepatocellular carcinoma	Chart review	2 years
Primary	Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	Baseline
Primary	Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	6 months
Primary	Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	1 year
Primary	Hand grip strength (kg)	Measured at each visit with a hand-grip dynamometer	18 months
Primary	Muscle function	Measured using the validated Short Physical Performance Battery.	Baseline
Primary	Muscle function	Measured using the validated Short Physical Performance Battery.	6 months
Primary	Muscle function	Measured using the validated Short Physical Performance Battery.	1 year
Primary	Muscle function	Measured using the validated Short Physical Performance Battery.	18 months
Primary	Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	Baseline
Primary	Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	6 months
Primary	Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	1 year
Primary	Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	18 months
Primary	Child-Pugh score	A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy	2 year
Primary	MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	Baseline
Primary	MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	6 months
Primary	MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	1 year
Primary	MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	18 months
Primary	MELD-score	A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium	2 years
Secondary	Death	Chart review	6 months
Secondary	Death	Chart review	1 year
Secondary	Death	Chart review	18 months
Secondary	Death	Chart review	2 years
Secondary	Esophageal varices	Assessed by gastroscopy and captured through chart review.	Baseline
Secondary	Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	6 months
Secondary	Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	1year
Secondary	Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	18 months
Secondary	Development of Esophageal varices	Assessed by gastroscopy and captured through chart review.	2 years
Secondary	Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	Baseline
Secondary	Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	6 months
Secondary	Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	1 year
Secondary	Liver stiffness by Fibroscan (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	18 months
Secondary	Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	Baseline
Secondary	Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	6 months
Secondary	Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	1 year
Secondary	Liver stiffness by MRE (kPa)	Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.	18 months
Secondary	Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	Baseline
Secondary	Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	6 months
Secondary	Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	1 year
Secondary	Spleen volume (ml)	A surrogate marker for portal hypertension and measured by MR.	18 months
Secondary	Quality of life (Questionnaire)	EQ-5D-5L	Baseline
Secondary	Quality of life (Questionnaire)	EQ-5D-5L	6 months
Secondary	Quality of life (Questionnaire)	EQ-5D-5L	1 year
Secondary	Quality of life (Questionnaire)	EQ-5D-5L	18 months
Secondary	Quality of life (Questionnaire)	Short Health Scale-liver	Baseline
Secondary	Quality of life (Questionnaire)	Short Health Scale-liver	6 months
Secondary	Quality of life (Questionnaire)	Short Health Scale-liver	1 year
Secondary	Quality of life (Questionnaire)	Short Health Scale-liver	18 months