Clinical trial NCT03186859: Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)
Official title: Effects of Dietary Intervention and Surgery on NAFLD (Non-Alcoholic Fatty Liver Disease)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Non Alcoholic Fatty Liver
Bariatric Surgery Candidate
Obesity, Morbid
Keywords: non-alcoholic fatty liver disease
bariatric surgery
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Change in liver fat content
timeFrame: 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:
measure: Hepatic fatty acid synthesis
timeFrame: liver biopsy taken during SG or RYGB
measure: Changes in relative contributions of pathways involved in lipid homeostasis
timeFrame: 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
measure: Changes in fasting and postprandial plasma lipid concentration
timeFrame: 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
measure: Changes in fasting and postprandial plasma glucose concentration
timeFrame: 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
measure: Change in the incorporation of 13C (from dietary fat) into CO2
timeFrame: 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
measure: Expression changes (gene/protein) in adipose tissue biopsies
timeFrame: 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
measure: Change in fat mass
timeFrame: 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
measure: Change in lean mass
timeFrame: 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
measure: Change in functional strength
timeFrame: 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
measure: changes in fasting and post-prandial peptides/proteins (e.g. PYY, GLP-1, insulin)
timeFrame: 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
measure: change in weight
timeFrame: 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
measure: change in body mass index (BMI)
timeFrame: 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
measure: change in status of metabolic diseases (e.g. diabetes) / metabolic disease risk scores
timeFrame: 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
measure: complications, re-operation, mortality
timeFrame: 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
measure: changes in subcutaneous, visceral and pancreatic fat
timeFrame: 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
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
affiliation: University of Oxford
name: Jeremy Tomlinson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: