Non-Alcoholic Fatty Liver DiseaseEDISONNCT03186859
Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)
A study testing Roux-en-Y Gastric Bypass (RYGB) surgery and Sleeve Gastrectomy (SG) surgery in people with Non-Alcoholic Fatty Liver Disease and Non Alcoholic Fatty Liver, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver, Bariatric Surgery Candidate
- What is being tested?
- Roux-en-Y Gastric Bypass (RYGB) surgery and Sleeve Gastrectomy (SG) surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Jun 2017to 30 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver, Bariatric Surgery Candidate, Obesity, Morbid
- Being tested
- Roux-en-Y Gastric Bypass (RYGB) surgery, Sleeve Gastrectomy (SG) surgery
- Keywords
- non-alcoholic fatty liver disease, bariatric surgery
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity, Morbid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roux-en-Y Gastric Bypass (RYGB) surgeryProcedure or surgery
RYGB operation using surgeons' standard technique
Sleeve Gastrectomy (SG) surgeryProcedure or surgery
SG surgery using surgeons' standard technique
| Study group | Role | What they receive |
|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) surgery | Active comparator | Not described Receives: Procedure: Roux-en-Y Gastric Bypass (RYGB) surgery |
| Sleeve Gastrectomy (SG) surgery | Active comparator | Not described Receives: Procedure: Sleeve Gastrectomy (SG) surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fat content
Change in liver fat content as measured on MRI scan +/- fibroscan
Measured: 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
Secondary outcomes (15)
Hepatic fatty acid synthesis
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
Measured: liver biopsy taken during SG or RYGB
Changes in relative contributions of pathways involved in lipid homeostasis
measured using mathematical modelling of results from stable isotope mixed meal test
Measured: 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
Changes in fasting and postprandial plasma lipid concentration
measured using a clinical analyser (in fasting states and in response to mixed meal test)
Measured: 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
Changes in fasting and postprandial plasma glucose concentration
measured using a clinical analyser measured using a clinical analyser (in fasting state and in response to mixed meal test)
Measured: 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 the incorporation of 13C (from dietary fat) into CO2
measured using a breath analyser (in fasting state and in response to mixed meal test)
Measured: 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
Expression changes (gene/protein) in adipose tissue biopsies
measured using techniques such as quantitative real-time PCR (polymerase chain reaction) and ELISA (enzyme- linked immunosorbent assay)
Measured: 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 fat mass
Proportional (% relative to baseline and lean mass) and absolute changes measured using DXA scan and bioimpedence analysis
Measured: 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 lean mass
Proportional (% relative to baseline and fat mass) and absolute changes measured using DXA scan and bioimpedence analysis
Measured: 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 functional strength
measured using hand dynamometer
Measured: 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
changes in fasting and post-prandial peptides/proteins (e.g. PYY, GLP-1, insulin)
measured using ELISA (in fasting state and in response to mixed meal test)
Measured: 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 weight
measured in kilograms using weighing scales
Measured: 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 body mass index (BMI)
weight measured in kilograms using weighing scales and combined with height in metres to report BMI in kg/m^2
Measured: 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 status of metabolic diseases (e.g. diabetes) / metabolic disease risk scores
measured with blood tests (e.g. hba1c), by recording clinical changes including medication requirements and clinical data (e.g. blood pressure)
Measured: 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
complications, re-operation, mortality
clinical events will be recorded
Measured: 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
changes in subcutaneous, visceral and pancreatic fat
measured on MRI scan
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start9 Jun 2017
- Primary completion30 Aug 2020
- Study completion30 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeremy Tomlinson, MD PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03186859
- Sponsor's protocol ID
- 219190
- Acronym
- EDISON
- Status last verified
- Mar 2020
- First submitted
- 23 May 2017
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)
- ClinicalTrials.gov ID
- NCT03186859
- Acronym / sponsor ID
- EDISON / 219190
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver, Bariatric Surgery Candidate, Obesity, Morbid
- Keywords
- non-alcoholic fatty liver disease, bariatric surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 9 Jun 2017 (actual)
- Primary completion
- 30 Aug 2020 (actual)
- Study completion
- 30 Aug 2020 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) surgery | Active comparator | Procedure: Roux-en-Y Gastric Bypass (RYGB) surgery |
| Sleeve Gastrectomy (SG) surgery | Active comparator | Procedure: Sleeve Gastrectomy (SG) surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) surgeryRYGB operation using surgeons' standard technique | Procedure or surgery | Roux-en-Y Gastric Bypass (RYGB) surgery |
| Sleeve Gastrectomy (SG) surgerySG surgery using surgeons' standard technique | Procedure or surgery | Sleeve Gastrectomy (SG) surgery |
Primary outcome
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
15 secondary outcomes
Hepatic fatty acid synthesis
Time frame: liver biopsy taken during SG or RYGB
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Tomlinson, MD PhD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Roux-en-Y Gastric Bypass (RYGB) surgery and Sleeve Gastrectomy (SG) surgery in people with Non-Alcoholic Fatty Liver Disease and Non Alcoholic Fatty Liver, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.