MRI and Stable Isotope Tracer Studies for Detecting the Progression of Non-Alcoholic Steatohepatitis (NASH)

NCT04227782 | Active Not Recruiting DMC

• 1 other identifier: MRI-DETECT
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

One-third of the world's population suffers from Non-Alcoholic Fatty Liver Disease (NAFLD), that is a disease with an accumulation of fat in the liver. Some patients with NAFLD will progress in their disease to develop inflammation, scarring of the liver tissue, and cirrhosis that can lead to liver failure. The mechanisms of the disease and its progression are still not fully understood. It is therefore critical to find early markers that can identify the patients that will progress so that they can be treated early. A compound called L-carnitine, synthesised in the body from two amino acids; lysine and methionine, is critical for fat metabolism. Some studies have shown that it is decreased in liver disease patients and that L-carnitine supplementation can protect the liver function. This study aims to increase the understanding of the mechanisms behind NAFLD disease progression through its different stages. This may help diagnostic methods to be developed to predict the patients at risk for developing severe liver disease. Furthermore, fat metabolism and L-carnitine levels will be established in the different disease stages to evaluate whether fat metabolism could be compromised. Magnetic Resonance Imaging (MRI) will be used for imaging of the whole liver and the heart to investigate metabolism and function non-invasively. Whole-body metabolism and how carbohydrates are taken up from diets are converted to fats in the body will be explored using stable isotope labelling. This study will recruit 30 participants with NAFLD; 10 each for low-risk NALFD, biopsy-proven NASH and compensated NASH cirrhosis. Participants will undergo MRI, followed by a stable isotope labelled study, where through blood- and breathe samples, metabolism will be investigated. An additional 10 healthy participants will be assessed using MR techniques to assess whether an injection of L-carnitine can lead to increase of L-carnitine in the liver such that it can be detected by MR. This is to validate a methodology prior to using it in NAFLD participants.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

magnetic resonance spectroscopy; magnetic resonance imaging; isotope tracer studies; fatty acid oxidation; de-novo lipogenesis; liver phosphorus MR spectroscopy

Outcome Measures

Primary Outcomes (1)

• Differences in whole-body fatty acid oxidation in a stable isotope labelled postprandial study day in participant groups.

  Changes in the incorporation of 13C (from dietary fat or sugar) into CO2 measured using a breath analyser, as a marker of whole-body dietary fatty acid/glucose oxidations.To explore whole-body fatty acid oxidation in individuals with simple steatosis, NASH and NASH with Cirrhosis

  baseline

Secondary Outcomes (4)

• Intrahepatic fatty acid synthesis in a stable isotope labelled postprandial study day in participant groups

  baseline

• Cardiac Function using MRI in participant groups

  baseline

• Difference in liver metabolites using MRS in participant groups

  baseline

• Difference in heart metabolites using MRS in participant groups

  baseline

Study Arms (4)

NAFLD

Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study

NASH

Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study

Cirrhosis

Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study

Healthy Volunteers

Diagnostic Test: Magnetic Resonance Imaging

Interventions

Magnetic Resonance Imaging DIAGNOSTIC_TEST

Magnetic Resonance Imaging

Also known as: magnetic resonance spectroscopy

Cirrhosis; Healthy Volunteers; NAFLD; NASH

Stable Isotope Study OTHER

Stable Isotope study

Cirrhosis; NAFLD; NASH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Population is patients with Non-alcoholic Fatty Liver Disease (NAFLD), either with simple steatosis, NASH or cirrhosis

You may qualify if:

• Aged ≥18
• In cases where histologic evidence is needed, the pathologist evaluation of a liver biopsy should be obtained within 90 days prior to screening.
• Participants with simple steatosis
• Findings of fatty liver on ultrasound in patients with low risk of NASH or advanced fibrosis defined as liver stiffness measurement \<8kPa.
• Participants with NASH:
• o Liver biopsy that shows presence of all the features of NASH (≥ 5% steatosis, lobular inflammation and hepatocyte ballooning) and without liver cirrhosis. Low-grade fibrosis are allowed.
• Participants with NASH cirrhosis:
• Liver biopsy that shows features of NASH cirrhosis. Historical liver biopsies will be acceptable provided there has been no significant weight loss (\> 5% of body weight) between the time of biopsy and recruitment, OR
• Presence of metabolic comorbidities and clinical (stigmata of chronic liver disease), radiological (e.g. irregular liver edge, features of portal hypertension), laboratory (deranged clotting, low platelet count) and non-invasive test results consistent with liver cirrhosis (e.g. liver stiffness \>20kPa).

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• For the albumin1 infusion: At screening individuals are asked about any allergies and in excluded to the albumin infusion in case of egg allergy. In case of lactose intolerance, milk will be exchanged to a lactosefree non-dairy form.
• Contraindication to MRI
• History of alcoholism or a greater than recommended weekly alcohol intake (14 units per week)
• Liver disease other than NAFLD (chronic viral hepatitis B or C, autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, Wilson's disease, alpha 1 antitrypsin deficiency, drug induced liver injury)
• Pregnant/Planning to get pregnant
• Low haemoglobin (NAFLD participants), women with Hb \< 11g/l and men with Hb \<12g/l will be excluded
• Unwillingness to refrain from blood donations in the specified period (NAFLD participants)
• Extensive tattooing covering the MRI scanning area

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

University of Oxford

Oxford, Oxfordshire, United Kingdom

Location

Related Publications (1)

• Savic D, Mozes FE, Green PG, Burrage MK, Kjaer MS, Hodson L, Neubauer S, Pavlides M, Valkovic L. Detection and alterations of acetylcarnitine (AC) in human liver by 1 H MRS at 3T after supplementation with l-carnitine. Magn Reson Med. 2023 Apr;89(4):1314-1322. doi: 10.1002/mrm.29544. Epub 2022 Dec 27.

  PMID: 36573435 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum, plasma, urine

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Magnetic Resonance Imaging; Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Radionuclide Imaging; Diagnostic Techniques, Radioisotope

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 14, 2020
• Study Start: March 1, 2020
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 16, 2024

Record last verified: 2023-11

Locations

GB (1)