Skip to main content
OpenTrials
Completed

NCT Number: NCT03186859

Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)

Approximately 90% of people undergoing bariatric surgery have NAFLD, which is a condition where fat accumulates in the liver and can lead to inflammation and scarring. It mostly causes no symptoms, however, in the most advanced cases there is an increased risk of liver cancer or liver failure.

NAFLD is currently managed by weight loss and treating associated diseases such as diabetes. No medicines have been licensed to directly treat it but bariatric surgery has been shown to be usually beneficial, although it is unknown whether some operations are better than others. It is also unclear whether this is due to general weight loss or other factors.

This study will be conducted in a hospital setting and aims to determine what changes in liver fat and fat processing occur after pre-operative low calorie diet and the two most common types of bariatric surgery (Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Participants will have ten study visits, four of which may be combined with NHS appointments. Participants will undergo investigations including MRI scans to measure changes in NAFLD and DEXA scans to measure changes in fat and fat-free mass (FFM). Participants will also undergo mixed meal testing to which stable isotopes (deuterated water and 13c-palmitate) will be added to allow changes in fat processing to be detected. In addition to samples taken as part of NHS care, blood, urine, liver and fat (visceral and subcutaneous (abdominal and gluteal)) will be used for research. Visits will take place before and after low calorie diet and bariatric surgery.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Non-Alcoholic Fatty Liver Disease Bariatric Surgery Candidate Body Weight Digestive System Diseases Fatty Liver Liver Diseases Non Alcoholic Fatty Liver Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Morbid Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Oxford

Oxford, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Bariatric surgery is already planned for the participant
  • Participant is willing and able to give informed consent for participation in the study.
  • Aged ≥18 or ≤75 years.
  • Body Mass Index ≥35 ≤55 kg/m2

Exclusion criteria

  • Contraindication to MRI
  • Prior or current participation in a CTIMP that could affect study results
  • History of alcoholism or a greater than recommended weekly alcohol intake (14 units per week)
  • History of albumin allergy
  • Anticoagulant treatment
  • Pregnant or nursing mothers
  • Type 2 Diabetes
  • A liver disease other than NAFLD
  • Histological confirmation of lack of NAFLD on liver biopsy
  • Large hiatus hernia (that would prohibit Sleeve Gastrectomy)
  • Active gastrooesophageal reflux disease (that would prohibit Sleeve Gastrectomy)
  • Active malabsorptive intestinal disease (that would prohibit Roux-en-Y Gastric Bypass surgery)

Treatment and study plan

Roux-en-Y Gastric Bypass (RYGB) surgery

Procedure

RYGB operation using surgeons' standard technique

Sleeve Gastrectomy (SG) surgery

Procedure

SG surgery using surgeons' standard technique

Primary outcomes

  1. Change in liver fat content

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    Change in liver fat content as measured on MRI scan +/- fibroscan

Secondary outcomes

  1. Hepatic fatty acid synthesis

    Time frame: liver biopsy taken during SG or RYGB

    measured by incorporation of 2H2 palmitate from 2H2O into very low density lipoprotein triglyceride (VLDL-TG) and contribution of de novo lipogenesis and uptake and re-esterification to the hepatic triglyceride pool in liver biopsy

  2. Changes in relative contributions of pathways involved in lipid homeostasis

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using mathematical modelling of results from stable isotope mixed meal test

  3. Changes in fasting and postprandial plasma lipid concentration

    Time frame: Baseline measurements just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using a clinical analyser (in fasting states and in response to mixed meal test)

  4. Changes in fasting and postprandial plasma glucose concentration

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using a clinical analyser measured using a clinical analyser (in fasting state and in response to mixed meal test)

  5. Change in the incorporation of 13C (from dietary fat) into CO2

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using a breath analyser (in fasting state and in response to mixed meal test)

  6. Expression changes (gene/protein) in adipose tissue biopsies

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using techniques such as quantitative real-time PCR (polymerase chain reaction) and ELISA (enzyme- linked immunosorbent assay)

  7. Change in fat mass

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    Proportional (% relative to baseline and lean mass) and absolute changes measured using DXA scan and bioimpedence analysis

  8. Change in lean mass

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    Proportional (% relative to baseline and fat mass) and absolute changes measured using DXA scan and bioimpedence analysis

  9. Change in functional strength

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using hand dynamometer

  10. changes in fasting and post-prandial peptides/proteins (e.g. PYY, GLP-1, insulin)

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured using ELISA (in fasting state and in response to mixed meal test)

  11. change in weight

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured in kilograms using weighing scales

  12. change in body mass index (BMI)

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    weight measured in kilograms using weighing scales and combined with height in metres to report BMI in kg/m^2

  13. change in status of metabolic diseases (e.g. diabetes) / metabolic disease risk scores

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured with blood tests (e.g. hba1c), by recording clinical changes including medication requirements and clinical data (e.g. blood pressure)

  14. complications, re-operation, mortality

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    clinical events will be recorded

  15. changes in subcutaneous, visceral and pancreatic fat

    Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB

    measured on MRI scan

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Registry information

Acronym: EDISON

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Jun 14, 2017
Registry last updated
May 10, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.