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The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease (FATFUNgenes)

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ClinicalTrials.gov Identifier: NCT04040595
Recruitment Status : Recruiting
First Posted : July 31, 2019
Last Update Posted : July 31, 2019
Sponsor:
Collaborators:
University of Exeter
NIHR Exeter Clinical Research Facility
Information provided by (Responsible Party):
Royal Devon and Exeter NHS Foundation Trust

Brief Summary:

Obesity is a major risk factor for Type 2 diabetes. However, two obese people of the same height and weight can have very different risks of the condition. As a greater proportion of the population is becoming obese, scientists need to understand more about why some people develop Type 2 diabetes at lower weight and why some people stay healthy despite being obese. The investigators and others provided evidence for genetic factors associated with higher weight for a given height but lower risk of diabetes, lower cholesterol and fat levels, lower blood pressure and lower risk of heart disease. The investigators showed that people who carry these genetic factors are able to store extra fat in a safe place, which is under the skin, as they gain weight. The proposed project aims to establish whether or not these genetic factors are associated with better development and function of fat tissue in storing extra fat. It is thought that a healthy and functional fat tissue in the human body has a key role in modifying the risk of diseases such as Type 2 diabetes, heart disease and hypertension.

Volunteers from Exeter 10,000 who gave their permission to contact them about further research will be recruited to the study. In those that agree, detailed body size measures, including body composition assessments by the BodPodTM machine will be recorded, a blood sample will be collected, and a small subcutaneous abdominal fat biopsy will be collected to measure fat cell size and from which a sample will be stored for future analyses. The results between people with and without the particular genetic changes of interest will be compared.

Knowing more about these genetic changes and how fat cells work could help to improve understanding of the factors that predispose, delay or protect obese individuals from Type 2 diabetes and other metabolic disturbances.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Procedure: Abdominal fat biopsy Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Intervention Model: Single Group Assignment
Intervention Model Description:

Anthropometry:

  • Baseline data including Height (m), Weight (kg), Waist (cm) and Hip (cm) circumference will be recorded.
  • Skin fold measurements (mm) from biceps, triceps, subscapular, and suprailiac regions
  • Detailed body fat measures will be obtained from the BodPodTM.

Medical history:

• including current medications and lifestyle information (smoking/alcohol).

Blood sample:

• Up to 20 ml venous blood sample for HbA1c and storage for analysis of biomarkers of adiposity.

Abdominal fat biopsy: for adipocyte measurements and store a sample for future analyses.

A sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips.

Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease
Actual Study Start Date : March 7, 2019
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Adipocyte measurement
Abdominal fat biopsy
Procedure: Abdominal fat biopsy
A sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx 15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips.




Primary Outcome Measures :
  1. Mean adipocyte size (µm2) assessed using Image J software. [ Time Frame: Within 12 months of recruitment date of final participant ]
    ImageJ is a cross-platform image analysis tool developed to measure particle/cell size and will be used here to measure adipocyte size to test whether or not individuals carrying a high genetic load of "favourable adiposity" alleles have smaller subcutaneous fat cells.


Secondary Outcome Measures :
  1. Adipose tissue expression of genes that are markers of adipogenesis (PPARy, CREBP). [ Time Frame: Within 12 months of recruitment date of final participant ]
    This secondary outcome is the adipocytes' gene expression measures of adipogenesis.

  2. Adipose tissue expression of genes that are markers of fibrosis (SPARC, collagens, TGFbeta, LOX). [ Time Frame: Within 12 months of recruitment date of final participant ]
    This secondary outcome is the adipocytes' gene expression measures of fibrosis.

  3. Adipose tissue expression of genes that are determinants of adipose inflammation (IL-1beta, IL-6, and 8, TNFalpha, MCP-1/CCL2). [ Time Frame: Within 12 months of recruitment date of final participant ]
    This secondary outcome is the adipocytes' gene expression measures of adipose inflammation.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Demographics: Age 18-75 inclusive
  • Ethnicity: Reflective of local demographic
  • Mental capacity: Willing and able to provide informed consent

Exclusion Criteria:

  • Medical history: History of bariatric surgery and recent significant weight loss/gain (+/- 3 kgs/ half a stone in the last 3 months); connective tissue disease, pregnancy and lactation (if women are recruited).
  • Medications: Currently prescribed oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
  • Mental capacity: Unable/unwilling to provide informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04040595


Contacts
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Contact: Michelle Hudson, BSc +44(0)1392 408183 m.hudson@exeter.ac.uk
Contact: Hanieh Yaghootkar, PhD H.Yaghootkar@exeter.ac.uk

Locations
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United Kingdom
Royal Devon and Exeter NHS Foundation Trust / University of Exeter Recruiting
Exeter, Devon, United Kingdom, EX2 5DW
Contact: Michelle Hudson    +44 (0)1392 408183    m.hudson@exeter.ac.uk   
Contact: Andrew Pitt    +44 (0)1392 408190    a.pitt@exeter.ac.uk   
Principal Investigator: Timothy M Frayling (Professor), PhD         
Sub-Investigator: Hanieh Yaghootkar, PhD         
Sub-Investigator: Katarina Kos, PhD         
Sponsors and Collaborators
Royal Devon and Exeter NHS Foundation Trust
University of Exeter
NIHR Exeter Clinical Research Facility
Investigators
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Principal Investigator: Timothy Frayling, PhD University of Exeter

Publications:
Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, Clavel-Chapelon F, Crowe FL, Dekker JM, Fagherazzi G, Ferrannini E, Forouhi NG, Franks PW, Gavrila D, Giedraitis V, Grioni S, Groop LC, Kaaks R, Key TJ, Kühn T, Lotta LA, Nilsson PM, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Roswall N, Sacerdote C, Sala N, Sánchez MJ, Schulze MB, Siddiq A, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, Yaghootkar H; RISC study group; EPIC-InterAct consortium, McCarthy MI, Semple RK, Riboli E, Walker M, Ingelsson E, Frayling TM, Savage DB, Langenberg C, Wareham NJ. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes. 2014 Dec;63(12):4378-4387. doi: 10.2337/db14-0319. Epub 2014 Jun 19.

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Responsible Party: Royal Devon and Exeter NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04040595     History of Changes
Other Study ID Numbers: IRAS: 257693
105009 ( Other Grant/Funding Number: Diabetes UK )
19/SW/0012 ( Other Identifier: South West - Central Bristol Research Ethics Committee )
1909872 ( Other Identifier: The Royal Devon & Exeter NHS Foundation Trust )
First Posted: July 31, 2019    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Royal Devon and Exeter NHS Foundation Trust:
Type 2 diabetes
adipocyte
adipocyte tissue dysfunction
adiposity
favourable adiposity
gene expression
adipose tissue

Additional relevant MeSH terms:
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Heart Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cardiovascular Diseases