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

NCT03186859 | Completed

• 1 other identifier: 219190
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Fatty Liver; Bariatric Surgery Candidate; Obesity, Morbid

Keywords

non-alcoholic fatty liver disease; bariatric surgery

Outcome Measures

Primary Outcomes (1)

• Change in liver fat content

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

  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

  liver biopsy taken during SG or RYGB

• Changes in relative contributions of pathways involved in lipid homeostasis

  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

  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

  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

  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

Study Arms (2)

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

Interventions

Roux-en-Y Gastric Bypass (RYGB) surgery PROCEDURE

RYGB operation using surgeons' standard technique

Roux-en-Y Gastric Bypass (RYGB) surgery

Sleeve Gastrectomy (SG) surgery PROCEDURE

SG surgery using surgeons' standard technique

Sleeve Gastrectomy (SG) surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity, Morbid

Interventions

Gastric Bypass; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatric Surgery; Bariatrics; Obesity Management; Therapeutics; Gastroenterostomy; Anastomosis, Surgical; Digestive System Surgical Procedures

Study Officials

• Jeremy Tomlinson, MD PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: June 14, 2017
• Study Start: June 9, 2017
• Primary Completion: August 30, 2020
• Study Completion: August 30, 2020
• Last Updated: May 10, 2023

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)