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

NCT04059068 | Completed

• 1 other identifier: 19HH5303
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

macrophage; adipose tissue; fibroblast; liver disease; RNA sequencing

Outcome Measures

Primary Outcomes (1)

• Macrophage ligand-fibroblast receptor

  Macrophage ligand-fibroblast receptors that are assessed by single cell-RNA-sequencing

  3 years

Study Arms (6)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College NHS Trust

London, W2 1NY, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Adipose tissue (6-8g) Liver tissue (1g) Blood (10ml) The samples will be used for analysis specifically for RNA, protein or imaging. They will either be cryo-preserved or snap frozen to prevent them from perishing. They can be stored in liquid nitrogen or -80 deg Celcius freezer for up to 10 years.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases

Study Officials

• Jacques Behmoaras, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 16, 2019
• Study Start: September 1, 2019
• Primary Completion: September 5, 2023
• Study Completion: September 5, 2023
• Last Updated: December 6, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)