Macrophage-mediated Inflammation in White Adipose Tissue and Non-alcoholic Fatty Liver Disease.

December 5, 2023 updated by: Imperial College London

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, W2 1NY
        • Imperial College NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients who are attending the bariatric services at St Mary hospital and UGI services at Hammersmith Hospital, Imperial College Healthcare NHS Trust.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

Participants with:

  • alcohol consumption more than 10g of ethanol per day
  • viral Hepatitis infection
  • HIV
  • Autoimmune condition
  • genetic liver disease
  • other metabolic causes of liver disease
  • abnormal clotting
  • immunosuppressive medication
  • drugs that are known to precipitate hepatic steatosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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 the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Macrophage ligand-fibroblast receptor
Time Frame: 3 years
Macrophage ligand-fibroblast receptors that are assessed by single cell-RNA-sequencing
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Imperial College London

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jacques Behmoaras, PhD, Imperial College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 5, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 5, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 15, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19HH5303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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