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Trial record 26 of 342 for:    hepatic steatosis AND fat AND Nonalcoholic Fatty Liver

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

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ClinicalTrials.gov Identifier: NCT03186859
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Non Alcoholic Fatty Liver Bariatric Surgery Candidate Obesity, Morbid Procedure: Roux-en-Y Gastric Bypass (RYGB) surgery Procedure: Sleeve Gastrectomy (SG) surgery Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)
Actual Study Start Date : June 9, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Active Comparator: Roux-en-Y Gastric Bypass (RYGB) surgery Procedure: Roux-en-Y Gastric Bypass (RYGB) surgery
RYGB operation using surgeons' standard technique

Active Comparator: Sleeve Gastrectomy (SG) surgery Procedure: Sleeve Gastrectomy (SG) surgery
SG surgery using surgeons' standard technique




Primary Outcome Measures :
  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 Outcome Measures :
  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



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:   No
Criteria

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)

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): NCT03186859


Contacts
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Contact: Jeremy Tomlinson, MD PhD 0044 1865 857359 jeremy.tomlinson@ocdem.ox.ac.uk
Contact: Niall Dempster, MD 0044 751 5437956 niall.dempster@balliol.ox.ac.uk

Locations
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United Kingdom
University of Oxford Recruiting
Oxford, United Kingdom
Contact: Jeremy W Tomlinson, MD PhD    44(0)1865 857359    jeremy.tomlinson@ocdem.ox.ac.uk   
Contact: Leanne Hodson, PhD       leanne.hodson@ocdem.ox.ac.uk   
Sub-Investigator: Niall Dempster, MD         
Sub-Investigator: Garry Tan, MD         
Sub-Investigator: Bruno Sgromo, MD         
Sub-Investigator: Richard Gillies, MD         
Sponsors and Collaborators
University of Oxford
Investigators
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Principal Investigator: Jeremy Tomlinson, MD PhD University of Oxford

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03186859     History of Changes
Other Study ID Numbers: 219190
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
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 University of Oxford:
non-alcoholic fatty liver disease
bariatric surgery

Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Obesity, Morbid
Digestive System Diseases
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms