NCT05502198

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P50-P75 for all trials

Timeline
51mo left

Started Feb 2021

Longer than P75 for all trials

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress56%
Feb 2021Jun 2030

Study Start

First participant enrolled

February 1, 2021

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

February 15, 2022

Completed
6 months until next milestone

First Posted

Study publicly available on registry

August 16, 2022

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2025

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2030

Expected
Last Updated

August 24, 2023

Status Verified

August 1, 2023

Enrollment Period

4.4 years

First QC Date

February 15, 2022

Last Update Submit

August 21, 2023

Conditions

Liver CirrhosisHepatocellular CarcinomaSarcopeniaPortal Hypertension

Outcome Measures

Primary Outcomes (46)

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    Baseline

  • Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    6 months

  • Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    1 year

  • Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    18 months

  • Change from baseline Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    6 months

  • Change from 6 months Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    1 year

  • Change from 1 year Muscle fat infiltration (%) [MFI]

    MFI is a measure, using MR, of percentage of fat infiltration in the muscles (%).

    18 months

  • Presence of previous decompensation

    If the patient previously has had ascites, bleeding esophageal varices, or encephalopathy.

    Baseline

  • New episode of decompensation since baseline

    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.

    6 months

  • New episode of decompensation since 6 months

    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.

    1 year

  • New episode of decompensation since 1 year

    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.

    18 months

  • New episode of decompensation since 18 months

    If the patient has had an episode of ascites, bleeding esophageal varices, or encephalopathy.

    2 years

  • Hepatocellular carcinoma

    Detection of HCC by AMRI

    Baseline

  • Significant liver lesion

    LI-RADS 3-5

    Baseline

  • Significant liver lesion

    LI-RADS 3-5

    6 months

  • Significant liver lesion

    LI-RADS 3-5

    1 year

  • Significant liver lesion

    LI-RADS 3-5

    18 months

  • Hepatocellular carcinoma

    Detection of HCC by AMRI

    6 months

  • Hepatocellular carcinoma

    Detection of HCC by AMRI

    1 year

  • Hepatocellular carcinoma

    Detection of HCC by AMRI

    18 months

  • Hepatocellular carcinoma

    Chart review

    2 years

  • Hand grip strength (kg)

    Measured at each visit with a hand-grip dynamometer

    Baseline

  • Hand grip strength (kg)

    Measured at each visit with a hand-grip dynamometer

    6 months

  • Hand grip strength (kg)

    Measured at each visit with a hand-grip dynamometer

    1 year

  • Hand grip strength (kg)

    Measured at each visit with a hand-grip dynamometer

    18 months

  • Muscle function

    Measured using the validated Short Physical Performance Battery.

    Baseline

  • Muscle function

    Measured using the validated Short Physical Performance Battery.

    6 months

  • Muscle function

    Measured using the validated Short Physical Performance Battery.

    1 year

  • Muscle function

    Measured using the validated Short Physical Performance Battery.

    18 months

  • Child-Pugh score

    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy

    Baseline

  • Child-Pugh score

    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy

    6 months

  • Child-Pugh score

    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy

    1 year

  • Child-Pugh score

    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy

    18 months

  • Child-Pugh score

    A validated score to assess prognosis in liver cirrhosis. Includes: Albumin, Bilirubin, INR, Ascites, and Encephalopathy

    2 year

  • MELD-score

    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

    Baseline

  • MELD-score

    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

    6 months

  • MELD-score

    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

    1 year

  • MELD-score

    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

    18 months

  • MELD-score

    A validated score to assess prognosis in liver cirrhosis. Includes: Creatinine, INR, Bilirubin, and Sodium

    2 years

Secondary Outcomes (29)

  • Death

    6 months

  • Death

    1 year

  • Death

    18 months

  • Death

    2 years

  • Esophageal varices

    Baseline

  • +24 more secondary outcomes

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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.

You may qualify if:

  • 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

You may not qualify if:

  • Contraindications for MRI
  • Subjects suffering from primary sclerosing cholangitis (PSC)
  • Subjects diagnosed with Hepatic carcinoma (HCC)
  • Previous liver transplant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Department of Gastroenterology), District Hospital in Eksjö

Eksjö, 57581, Sweden

RECRUITING

Department of gastroenterology, County Hospital in Jönköping

Jönköping, 55185, Sweden

RECRUITING

Department of gastroenterology and hepatology

Linköping, Sweden

RECRUITING

Related Publications (1)

  • Nasr P, Forsgren M, Balkhed W, Jonsson C, Dahlstrom N, Simonsson C, Cai S, Cederborg A, Henriksson M, Stjernman H, Rejler M, Sjogren D, Cedersund G, Bartholoma W, Ryden I, Lundberg P, Kechagias S, Leinhard OD, Ekstedt M. A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol. BMC Gastroenterol. 2023 Dec 21;23(1):454. doi: 10.1186/s12876-023-03093-8.

    PMID: 38129794DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum Plasma Whole blood

MeSH Terms

Conditions

Liver CirrhosisCarcinoma, HepatocellularSarcopeniaHypertension, Portal

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteMuscular AtrophyNeuromuscular ManifestationsNeurologic ManifestationsNervous System DiseasesAtrophyPathological Conditions, AnatomicalSigns and Symptoms

Study Officials

  • Mattias Ekstedt, MD, PhD

    Linkoeping University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Mattias Ekstedt, MD, PhD

CONTACT

+46709296267mattias.ekstedt@liu.se

Mikael Forsgren, PhD

CONTACT

mikael.forsgren@amramedical.com

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

February 15, 2022

First Posted

August 16, 2022

Study Start

February 1, 2021

Primary Completion

June 30, 2025

Study Completion (Estimated)

June 30, 2030

Last Updated

August 24, 2023

Record last verified: 2023-08

Locations

SE(3)