Relevance of Sarcopenia in Advanced Liver Disease (ACCESS-ESLD)

• ClinicalTrials.gov Identifier: NCT05502198
• Recruitment Status: Recruiting
• First Posted: August 16, 2022
• Last Update Posted: August 24, 2023
• Sponsor: Linkoeping University
• Collaborator: Amra Medical AB
• Information provided by (Responsible Party): Mattias Ekstedt, Linkoeping University

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
Liver Cirrhosis; Hepatocellular Carcinoma; Sarcopenia; Portal Hypertension

Detailed 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

Study Design

• Study Type: Observational
• Estimated Enrollment: 150 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: February 1, 2021
• Estimated Primary Completion Date: June 30, 2025
• Estimated Study Completion Date: June 30, 2030

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Body composition (FFMVvcg) [ Time Frame: 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.
2. Body composition (FFMVvcg) [ Time Frame: 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.
3. Body composition (FFMVvcg) [ Time Frame: 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.
4. Body composition (FFMVvcg) [ Time Frame: 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.
5. Change from baseline Body composition (FFMVvcg) [ Time Frame: 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.
6. Change from 6 months Body composition (FFMVvcg) [ Time Frame: 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.
7. Change from 1 year Body composition (FFMVvcg) [ Time Frame: 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.
8. Muscle fat infiltration (%) [MFI] [ Time Frame: Baseline ]
   MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
9. Muscle fat infiltration (%) [MFI] [ Time Frame: 6 months ]
   MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
10. Muscle fat infiltration (%) [MFI] [ Time Frame: 1 year ]
    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
11. Muscle fat infiltration (%) [MFI] [ Time Frame: 18 months ]
    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
12. Change from baseline Muscle fat infiltration (%) [MFI] [ Time Frame: 6 months ]
    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
13. Change from 6 months Muscle fat infiltration (%) [MFI] [ Time Frame: 1 year ]
    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
14. Change from 1 year Muscle fat infiltration (%) [MFI] [ Time Frame: 18 months ]
    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).
15. Presence of previous decompensation [ Time Frame: Baseline ]
    If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.
16. New episode of decompensation since baseline [ Time Frame: 6 months ]
    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
17. New episode of decompensation since 6 months [ Time Frame: 1 year ]
    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
18. New episode of decompensation since 1 year [ Time Frame: 18 months ]
    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
19. New episode of decompensation since 18 months [ Time Frame: 2 years ]
    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.
20. Hepatocellular carcinoma [ Time Frame: Baseline ]
    Detection of HCC by AMRI
21. Significant liver lesion [ Time Frame: Baseline ]
    LI-RADS 3-5
22. Significant liver lesion [ Time Frame: 6 months ]
    LI-RADS 3-5
23. Significant liver lesion [ Time Frame: 1 year ]
    LI-RADS 3-5
24. Significant liver lesion [ Time Frame: 18 months ]
    LI-RADS 3-5
25. Hepatocellular carcinoma [ Time Frame: 6 months ]
    Detection of HCC by AMRI
26. Hepatocellular carcinoma [ Time Frame: 1 year ]
    Detection of HCC by AMRI
27. Hepatocellular carcinoma [ Time Frame: 18 months ]
    Detection of HCC by AMRI
28. Hepatocellular carcinoma [ Time Frame: 2 years ]
    Chart review
29. Hand grip strength (kg) [ Time Frame: Baseline ]
    Measured at each visit with a hand-grip dynamometer
30. Hand grip strength (kg) [ Time Frame: 6 months ]
    Measured at each visit with a hand-grip dynamometer
31. Hand grip strength (kg) [ Time Frame: 1 year ]
    Measured at each visit with a hand-grip dynamometer
32. Hand grip strength (kg) [ Time Frame: 18 months ]
    Measured at each visit with a hand-grip dynamometer
33. Muscle function [ Time Frame: Baseline ]
    Measured using the validated Short Physical Performance Battery.
34. Muscle function [ Time Frame: 6 months ]
    Measured using the validated Short Physical Performance Battery.
35. Muscle function [ Time Frame: 1 year ]
    Measured using the validated Short Physical Performance Battery.
36. Muscle function [ Time Frame: 18 months ]
    Measured using the validated Short Physical Performance Battery.
37. Child-Pugh score [ Time Frame: Baseline ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
38. Child-Pugh score [ Time Frame: 6 months ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
39. Child-Pugh score [ Time Frame: 1 year ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
40. Child-Pugh score [ Time Frame: 18 months ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
41. Child-Pugh score [ Time Frame: 2 year ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy
42. MELD-score [ Time Frame: Baseline ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
43. MELD-score [ Time Frame: 6 months ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
44. MELD-score [ Time Frame: 1 year ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
45. MELD-score [ Time Frame: 18 months ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium
46. MELD-score [ Time Frame: 2 years ]
    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

Secondary Outcome Measures :

1. Death [ Time Frame: 6 months ]
   Chart review
2. Death [ Time Frame: 1 year ]
   Chart review
3. Death [ Time Frame: 18 months ]
   Chart review
4. Death [ Time Frame: 2 years ]
   Chart review
5. Esophageal varices [ Time Frame: Baseline ]
   Assessed by gastroscopy and captured through chart review.
6. Development of Esophageal varices [ Time Frame: 6 months ]
   Assessed by gastroscopy and captured through chart review.
7. Development of Esophageal varices [ Time Frame: 1year ]
   Assessed by gastroscopy and captured through chart review.
8. Development of Esophageal varices [ Time Frame: 18 months ]
   Assessed by gastroscopy and captured through chart review.
9. Development of Esophageal varices [ Time Frame: 2 years ]
   Assessed by gastroscopy and captured through chart review.
10. Liver stiffness by Fibroscan (kPa) [ Time Frame: Baseline ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
11. Liver stiffness by Fibroscan (kPa) [ Time Frame: 6 months ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
12. Liver stiffness by Fibroscan (kPa) [ Time Frame: 1 year ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
13. Liver stiffness by Fibroscan (kPa) [ Time Frame: 18 months ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
14. Liver stiffness by MRE (kPa) [ Time Frame: Baseline ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
15. Liver stiffness by MRE (kPa) [ Time Frame: 6 months ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
16. Liver stiffness by MRE (kPa) [ Time Frame: 1 year ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
17. Liver stiffness by MRE (kPa) [ Time Frame: 18 months ]
    Liver stiffness is a surrogate marker for fibrosis stage, portal hypertension, and a prognostic marker.
18. Spleen volume (ml) [ Time Frame: Baseline ]
    A surrogate marker for portal hypertension and measured by MR.
19. Spleen volume (ml) [ Time Frame: 6 months ]
    A surrogate marker for portal hypertension and measured by MR.
20. Spleen volume (ml) [ Time Frame: 1 year ]
    A surrogate marker for portal hypertension and measured by MR.
21. Spleen volume (ml) [ Time Frame: 18 months ]
    A surrogate marker for portal hypertension and measured by MR.
22. Quality of life (Questionnaire) [ Time Frame: Baseline ]
    EQ-5D-5L
23. Quality of life (Questionnaire) [ Time Frame: 6 months ]
    EQ-5D-5L
24. Quality of life (Questionnaire) [ Time Frame: 1 year ]
    EQ-5D-5L
25. Quality of life (Questionnaire) [ Time Frame: 18 months ]
    EQ-5D-5L
26. Quality of life (Questionnaire) [ Time Frame: Baseline ]
    Short Health Scale-liver
27. Quality of life (Questionnaire) [ Time Frame: 6 months ]
    Short Health Scale-liver
28. Quality of life (Questionnaire) [ Time Frame: 1 year ]
    Short Health Scale-liver
29. Quality of life (Questionnaire) [ Time Frame: 18 months ]
    Short Health Scale-liver

Biospecimen Retention:   Samples With DNA

Serum Plasma Whole blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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. All etiologies of cirrhosis will be included except patients with primary sclerosing cholangitis.

Criteria

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

Contacts and Locations

Contacts

Contact: Mattias Ekstedt, MD, PhD; +46709296267; mattias.ekstedt@liu.se

Contact: Mikael Forsgren, PhD; mikael.forsgren@amramedical.com

Locations

Sweden

Department of Gastroenterology), District Hospital in Eksjö; Recruiting

Eksjö, Sweden, 57581

Contact: Martin Rejler, PhD, MD martin.rejler@rjl.se

Contact: Daniel Sjögren, MD daniel.sjogren@rjl.se

Principal Investigator: Martin Rejler, PhD, MD

Sub-Investigator: Daniel Sjögren, MD

Department of gastroenterology, County Hospital in Jönköping; Recruiting

Jönköping, Sweden, 55185

Contact: Henrik Stjernman, PhD, MD henrik.stjernman@rjl.se

Principal Investigator: Henrik Stjernman, PhD, MD

Department of gastroenterology and hepatology; Recruiting

Linköping, Sweden

Contact: Camilla Holmgren +46101030000 camilla.holmgren@regionostergotland.se

Sponsors and Collaborators

Linkoeping University

Amra Medical AB

Investigators

• Principal Investigator: Mattias Ekstedt, MD, PhD; Linkoeping University

More Information

• Responsible Party: Mattias Ekstedt, Associate Professor, Linkoeping University
• ClinicalTrials.gov Identifier: NCT05502198
• Other Study ID Numbers: 2020-07215
• First Posted: August 16, 2022
• Last Update Posted: August 24, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Liver Diseases; Liver Cirrhosis; Hypertension, Portal; Sarcopenia; Hypertension; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Vascular Diseases; Cardiovascular Diseases; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Fibrosis; Pathologic Processes; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical