Non-Alcoholic Fatty Liver DiseaseMRI-DetectNCT04227782
MRI and Stable Isotope Tracer Studies for Detecting the Progression of Non-Alcoholic Steatohepatitis (NASH)
An observational study of Non-Alcoholic Fatty Liver Disease, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Magnetic Resonance Imaging and Stable Isotope Study
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2020to 1 Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: Population is patients with Non-alcoholic Fatty Liver Disease (NAFLD), either with simple steatosis, NASH or cirrhosis
Who may be able to join
- 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
- Liver biopsy that shows features of simple steatosis and no signs of advanced fibrosis or NASH (F3) or cirrhosis (F4). Simple steatosis will be defined as the presence of lipid inclusions in ≥ 5% of hepatocytes without both of lobular inflammation and hepatocyte ballooning. Steatosis with either lobular inflammation or ballooning will be included in this category provided there is no bridging fibrosis (<F3 on the NASH CRN fibrosis classification system), OR
- 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:
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- 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).
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the detailed description
STUDY 1: Functional and Metabolic Parameters in participants with NAFLD Participants will undertake two study visits, within a 14-day period. One of the visits will involve MR assessments that will take up to three hours in total. The second visit will involve a postprandial study day using stable isotopes. Baseline samples will be taken from participants, and after they have been fed a standardised test meal to assess whole-body and liver specific postprandial metabolism - this visit will last up to eight hours.
Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) and stable isotope labelling are two methodologies to investigate in vivo metabolism and function non-invasively. MRI gives information about liver structure and tissue composition, and heart function. MRS can also evaluate tissue energetics and composition using spectroscopy. Stable isotope-labelling studies allow for the measurement of whole-body fatty acid oxidation and de-novo lipogenesis in the pre- and post-prandial state. These two methodologies will be used in our study to evaluate participants with different severity of NAFLD and could help elucidate how the disease progresses.
STUDY 2: MRI evaluation of L-carnitine In parallel to study 1, the physiological response to L-carnitine (50 mg/kg i.v.) will be investigated only in healthy participants with 1H MRS.
These participants will only take part in one visit, during which they will undergo a baseline MRI scan, followed by the injection of L-carnitine. The MRI/MRS will be repeated two hours after the injection. AC has previously been measured in skeletal muscle using 1H MRS. In this study it will be measured in the septum of the heart and in the liver pre and 2 hours post-injection of 50 mg/kg i.v. of L-carnitine.
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Being tested
- Magnetic Resonance Imaging, Stable Isotope Study
- Keywords
- magnetic resonance spectroscopy, magnetic resonance imaging, isotope tracer studies, fatty acid oxidation, de-novo lipogenesis, liver phosphorus MR spectroscopy
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingDiagnostic test
Also called magnetic resonance spectroscopy
Magnetic Resonance Imaging
Stable Isotope StudyOther
Stable Isotope study
| Study group | Role | What they receive |
|---|---|---|
| NAFLD | Not described Receives: Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study | |
| NASH | Not described Receives: Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study | |
| Cirrhosis | Not described Receives: Diagnostic Test: Magnetic Resonance Imaging; Other: Stable Isotope Study | |
| Healthy Volunteers | Not described Receives: Diagnostic Test: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline
Secondary outcomes (4)
Intrahepatic fatty acid synthesis in a stable isotope labelled postprandial study day in participant groups
Differences in hepatic fatty acid synthesis as measured by incorporation of 2H2 palmitate from 2H2O into very low density lipoprotein triglyceride (VLDL-TG) in participants with simple steatosis, NASH and NASH Cirrhosis.
Measured: baseline
Cardiac Function using MRI in participant groups
Comparison of the cardiac function as assessed by ejection fraction
Measured: baseline
Difference in liver metabolites using MRS in participant groups
Differences in hepatic energetics using 31P MRS comparing Pi/ATP ratio in participants with simple steatosis, NASH and NASH Cirrhosis.
Measured: baseline
Difference in heart metabolites using MRS in participant groups
Differences in cardiac fat content using 1H MRS in participants with simple steatosis, NASH and NASH Cirrhosis.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 Mar 2020
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227782
- Sponsor's protocol ID
- MRI-DETECT
- Acronym
- MRI-Detect
- Status last verified
- Nov 2023
- First submitted
- 19 Dec 2019
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 36573435
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI and Stable Isotope Tracer Studies for Detecting the Progression of Non-Alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT04227782
- Acronym / sponsor ID
- MRI-Detect / MRI-DETECT
- 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
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 14 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
STUDY 1: Functional and Metabolic Parameters in participants with NAFLD Participants will undertake two study visits, within a 14-day period. One of the visits will involve MR assessments that will take up to three hours in total. The second visit will involve a postprandial study day using stable isotopes. Baseline samples will be taken from participants, and after they have been fed a standardised test meal to assess whole-body and liver specific postprandial metabolism - this visit will last up to eight hours.
Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) and stable isotope labelling are two methodologies to investigate in vivo metabolism and function non-invasively. MRI gives information about liver structure and tissue composition, and heart function. MRS can also evaluate tissue energetics and composition using spectroscopy. Stable isotope-labelling studies allow for the measurement of whole-body fatty acid oxidation and de-novo lipogenesis in the pre- and post-prandial state. These two methodologies will be used in our study to evaluate participants with different severity of NAFLD and could help elucidate how the disease progresses.
STUDY 2: MRI evaluation of L-carnitine In parallel to study 1, the physiological response to L-carnitine (50 mg/kg i.v.) will be investigated only in healthy participants with 1H MRS.
These participants will only take part in one visit, during which they will undergo a baseline MRI scan, followed by the injection of L-carnitine. The MRI/MRS will be repeated two hours after the injection. AC has previously been measured in skeletal muscle using 1H MRS. In this study it will be measured in the septum of the heart and in the liver pre and 2 hours post-injection of 50 mg/kg i.v. of L-carnitine.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Population is patients with Non-alcoholic Fatty Liver Disease (NAFLD), either with simple steatosis, NASH or cirrhosis
Key inclusion criteria (10 listed)
- 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
- Liver biopsy that shows features of simple steatosis and no signs of advanced fibrosis or NASH (F3) or cirrhosis (F4). Simple steatosis will be defined as the presence of lipid inclusions in ≥ 5% of hepatocytes without both of lobular inflammation and hepatocyte ballooning. Steatosis with either lobular inflammation or ballooning will be included in this category provided there is no bridging fibrosis (<F3 on the NASH CRN fibrosis classification system), OR
- Findings of fatty liver on ultrasound in patients with low risk of NASH or advanced fibrosis defined as liver stiffness measurement <8kPa.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance ImagingAlso: magnetic resonance spectroscopyMagnetic Resonance Imaging | Diagnostic test | Cirrhosis, Healthy Volunteers, NAFLD, NASH |
| Stable Isotope StudyStable Isotope study | Other | Cirrhosis, NAFLD, NASH |
Primary outcome
Differences in whole-body fatty acid oxidation in a stable isotope labelled postprandial study day in participant groups.
Time frame: baseline
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
4 secondary outcomes
Intrahepatic fatty acid synthesis in a stable isotope labelled postprandial study day in participant groups
Time frame: baseline
Cardiac Function using MRI in participant groups
Time frame: baseline
Difference in liver metabolites using MRS in participant groups
Time frame: baseline
Difference in heart metabolites using MRS in participant groups
Time frame: baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Background: PubMed 36573435Savic 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-Alcoholic Fatty Liver Disease, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in whole-body fatty acid oxidation in a stable isotope labelled postprandial study day in participant groups. (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04227782, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.