Non-Alcoholic Fatty Liver DiseaseNCT04059068
Macrophage-mediated Inflammation in White Adipose Tissue and Non-alcoholic Fatty Liver Disease.
An observational study of Non-Alcoholic Fatty Liver Disease, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is present in one third of the population and due to its potential to cause irreversible liver damage and liver cancer, it is a significant health burden. There is a strong link between obesity and NALFD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2019to 5 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Study population: Patients who are attending the bariatric services at St Mary hospital and UGI services at Hammersmith Hospital, Imperial College Healthcare NHS Trust.
Who may be able to join
- Bariatric and Upper Gastrointestinal (UGI) surgery patients classified as obese or morbidly obese (BMI >30)
- Patients who attend UGI cancer services with a BMI <25
Who cannot join
- Participants with:
- alcohol consumption more than 10g of ethanol per day
- viral Hepatitis infection
- HIV
- Autoimmune condition
- genetic liver disease
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- other metabolic causes of liver disease
- abnormal clotting
- immunosuppressive medication
- drugs that are known to precipitate hepatic steatosis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Understanding the Role of Macrophage-mediated Inflammation in White Adipose Tissue and Liver Fibrosis
Non-alcoholic fatty liver disease (NAFLD) is present in one third of the population and due to its potential to cause irreversible liver damage and liver cancer, it is a significant health burden. There is a strong link between obesity and NALFD. As fat accumulates, the body is unable to process it, leading to unhealthy fat metabolism. Currently, other than lifestyle measures and better control of Type 2 Diabetes Mellitus (T2DM) with medication, there is no drug that can prevent or reverse the liver damage. Furthermore, there is no easy way to identify which person will go on to develop the liver damage.
Mounting evidence suggests that inflammation in the fat has a key role in driving liver damage, particularly by the immune cell called the macrophage. However, detailed mechanisms are lacking. Therefore, the aim of this proposal is to study obese patients with NAFLD to better understand the link between unhealthy fat metabolism and liver damage, focusing on identifying macrophage-derived drug targets which can potentially reverse the liver disease. Samples of fat and liver from patients who are having bariatric surgery at Imperial College Healthcare NHS Trust will be analysed to identify and target the inflammatory markers of unhealthy fat and NAFLD using genetic profiling techniques.
Read the detailed description
NAFLD is a huge health burden and can lead to liver damage,scarring and cancer, therefore gaining a further understanding of the mechanisms involved in causing liver damage is particularly important to identify drug targets that could reverse this process.
White adipose tissue (WAT) or fat fails to respond normally in obesity which leads to fat deposition in other organs, particularly the liver, and the fat tissue becomes inflamed. The inflammation in the fat is lead by specific immune cells called macrophages. This inflammatory state in the fat tissue is thought to be a precursor to liver inflammation and liver damage. This has been demonstrated in mouse models where the fat inflammatory cells contributed to liver inflammation and worsened liver damage, emphasising the importance of the relationship between fat tissue and the liver in NAFLD.
Liver damage or liver fibrosis is also the result of activation of these inflammatory cells, the macrophages, in the liver which drive scarring through cells called fibroblasts that lay down collagen. Therefore, understanding the interaction between the cells involved in inflammation (macrophages) and scarring (fibroblasts) in both the fat and the liver is key to identifying potential drug targets for reversal of this process.
|the investigators demonstrated, using an obese animal model, that the release of pro-fibrotic compounds called prostagladins from the fat macrophages is linked to NAFLD and liver inflammation. Based on these results the investigators aim to deepen the understanding of the link between fat and liver inflammation and damage specifically looking at cell interactions (the macrophage and fibroblast) by using genetic tests on liver and fat samples in obese participants.
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Keywords
- macrophage, adipose tissue, fibroblast, liver disease, RNA sequencing
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| NASH (non-alcoholic steatohepatitis) | Patients diagnosed with non-alcoholic steatohepatitis. | |
| NAFLD (non-alcoholic fatty liver disease) | Patients diagnosed with non-alcoholic fatty liver disease. | |
| Control | Patients with normal liver tissue. | |
| obese / high WAT inflammation and fibrosis | Patients who are obese with inflammed white adipose tissue and evidence of fibrosis. | |
| obese / low WAT inflammation and fibrosis | Patients who are obese with no evidence of inflammed white adipose tissue and no evidence of fibrosis. | |
| non- obese controls | Patients who are not obese. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrophage ligand-fibroblast receptor
Macrophage ligand-fibroblast receptors that are assessed by single cell-RNA-sequencing
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2019
- Study start1 Sep 2019
- Primary completion5 Sep 2023
- Study completion5 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jacques Behmoaras, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04059068
- Sponsor's protocol ID
- 19HH5303
- Status last verified
- Dec 2023
- First submitted
- 15 Aug 2019
- Last updated
- 6 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Role of Macrophage-mediated Inflammation in White Adipose Tissue and Liver Fibrosis
- ClinicalTrials.gov ID
- NCT04059068
- Acronym / sponsor ID
- 19HH5303
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Keywords
- macrophage, adipose tissue, fibroblast, liver disease, RNA sequencing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 5 Sep 2023 (actual)
- Study completion
- 5 Sep 2023 (actual)
- First posted
- 16 Aug 2019 (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.
Non-alcoholic fatty liver disease (NAFLD) is present in one third of the population and due to its potential to cause irreversible liver damage and liver cancer, it is a significant health burden. There is a strong link between obesity and NALFD. As fat accumulates, the body is unable to process it, leading to unhealthy fat metabolism. Currently, other than lifestyle measures and better control of Type 2 Diabetes Mellitus (T2DM) with medication, there is no drug that can prevent or reverse the liver damage. Furthermore, there is no easy way to identify which person will go on to develop the liver damage.
Mounting evidence suggests that inflammation in the fat has a key role in driving liver damage, particularly by the immune cell called the macrophage. However, detailed mechanisms are lacking. Therefore, the aim of this proposal is to study obese patients with NAFLD to better understand the link between unhealthy fat metabolism and liver damage, focusing on identifying macrophage-derived drug targets which can potentially reverse the liver disease. Samples of fat and liver from patients who are having bariatric surgery at Imperial College Healthcare NHS Trust will be analysed to identify and target the inflammatory markers of unhealthy fat and NAFLD using genetic profiling techniques.
Detailed description
NAFLD is a huge health burden and can lead to liver damage,scarring and cancer, therefore gaining a further understanding of the mechanisms involved in causing liver damage is particularly important to identify drug targets that could reverse this process.
White adipose tissue (WAT) or fat fails to respond normally in obesity which leads to fat deposition in other organs, particularly the liver, and the fat tissue becomes inflamed. The inflammation in the fat is lead by specific immune cells called macrophages. This inflammatory state in the fat tissue is thought to be a precursor to liver inflammation and liver damage. This has been demonstrated in mouse models where the fat inflammatory cells contributed to liver inflammation and worsened liver damage, emphasising the importance of the relationship between fat tissue and the liver in NAFLD.
Liver damage or liver fibrosis is also the result of activation of these inflammatory cells, the macrophages, in the liver which drive scarring through cells called fibroblasts that lay down collagen. Therefore, understanding the interaction between the cells involved in inflammation (macrophages) and scarring (fibroblasts) in both the fat and the liver is key to identifying potential drug targets for reversal of this process.
|the investigators demonstrated, using an obese animal model, that the release of pro-fibrotic compounds called prostagladins from the fat macrophages is linked to NAFLD and liver inflammation. Based on these results the investigators aim to deepen the understanding of the link between fat and liver inflammation and damage specifically looking at cell interactions (the macrophage and fibroblast) by using genetic tests on liver and fat samples in obese participants.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| NASH (non-alcoholic steatohepatitis) | – | –Patients diagnosed with non-alcoholic steatohepatitis. |
| NAFLD (non-alcoholic fatty liver disease) | – | –Patients diagnosed with non-alcoholic fatty liver disease. |
| Control | – | –Patients with normal liver tissue. |
| obese / high WAT inflammation and fibrosis | – | –Patients who are obese with inflammed white adipose tissue and evidence of fibrosis. |
| obese / low WAT inflammation and fibrosis | – | –Patients who are obese with no evidence of inflammed white adipose tissue and no evidence of fibrosis. |
| non- obese controls | – | –Patients who are not obese. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are attending the bariatric services at St Mary hospital and UGI services at Hammersmith Hospital, Imperial College Healthcare NHS Trust.
Key inclusion criteria (2 listed)
- Bariatric and Upper Gastrointestinal (UGI) surgery patients classified as obese or morbidly obese (BMI >30)
- Patients who attend UGI cancer services with a BMI <25
Key exclusion criteria (10 listed)
- alcohol consumption more than 10g of ethanol per day
- viral Hepatitis infection
- HIV
- Autoimmune condition
- genetic liver disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Macrophage ligand-fibroblast receptor
Time frame: 3 years
Macrophage ligand-fibroblast receptors that are assessed by single cell-RNA-sequencing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2023.
- Individual participant dataSharing planned: No
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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.
Jacques Behmoaras, PhD principal investigator
Imperial College London
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 Imperial College London 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 2 inclusion and 10 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: finished, as of the sponsor's last update on 6 Dec 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Macrophage ligand-fibroblast receptor (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Dec 2023; AzTrials last refreshed its copy on 7 Nov 2026.