Vertical Sleeve Gastrectomy and Lifestyle Modification for the Treatment of Non-Alcoholic Steatohepatitis

NCT03587831 | Recruiting DMC

• 1 other identifier: SURG-2018-26636
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Participants meeting study entry criteria are randomized with equal probability to one of two study groups: (1) Lifestyle modification or (2) Vertical Sleeve Gastrectomy (VSG) with Iifestyle modification, followed for 12 months. The primary goal for the trial is to determine if the investigators can recruit, randomize, and retain participants to perform invasive and non-invasive measurements of NASH and fibrosis, deliver lifestyle modification and demonstrate the safety of VSG. The investigators wish to also understand which of these two interventions is more effective in achieving, 12 months after entry into the trial, a reduction in NAS composed of the non-weighted scores: (1) steatosis 0-3 (2) Inflammation 0-3 and (3) ballooning 0-2. Secondary goals include comparing the two treatment groups for changes in other measured outcomes including MRI assessments of intrahepatic triglyceride and liver elasticity and serum markers. As a pilot study, a sample size of 20 in each group should offer significant information as to the difference in NAS score reduction between to two groups and achieve adequate power to distinguish clinically significant changes in the primary and secondary outcome measures. These data support the overarching objective i.e. to provide evidence that a larger, longer-term clinical outcomes trial is feasible. A goal is for a longer term follow up for 5 years to assess the durability of treatment effects and treatment differences.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Histologic improvements in NAFLD Activity Score (NAS)

  The scale used is NAS - this is the NAFLD (Nonalcoholic Fatty Liver Disease) Activity Score. The NAS was developed to provide a numerical score for patients who most likely have NASH. Accordingly, NAS is the sum of the separate scores for steatosis (0-3), hepatocellular ballooning (0-2) and lobular inflammation (0-3). NAS scores of 0-2 are largely considered not diagnostic of NASH, scores of 3-4 are often considered not diagnostic, borderline, or potentially positive for NASH. Scores of 5-8 are largely considered diagnostic of NASH. It is expected that the addition of VSG to lifestyle modification will result in more robust histologic improvements in NAFLD Activity Score (NAS) compared to lifestyle modification alone.

  Month 12

Study Arms (2)

VSG + LSM

EXPERIMENTAL

Procedure/Surgery: Vertical Sleeve Gastrectomy will be performed using five laparoscopic ports. The short gastric and epiploic vessels will be taken down With a 40 French Bougie in place, the greater curvature will be excised starting 6 cm proximal to the pylorus. Behavioral: Lifestyle Modification Counseling - The intensive lifestyle intervention will align with methods listed in the LSM arm description. However, participants assigned to the VSG will not have calorie ceilings during the first 6 months of rapid weight loss, and they will receive additional instruction regarding food volume and adequate protein intake.

Procedure: Vertical Sleeve Gastrectomy; Behavioral: Lifestyle Modification Counseling

LSM

ACTIVE COMPARATOR

Behavioral: Lifestyle Modification Counseling - The intensive lifestyle intervention is modeled after the LookAHEAD trial, with modules modified for participants undergoing surgery, and designed to produce maximum achievable weight loss. Both groups will increase their level of moderate-intensity physical activity (such as walking) to a total of 325 minutes per week. All lifestyle-medical management participants will be given calorie intake targets of 1200, 1500, or 1800 kilocalories per day, depending on body weight, with the goal of producing a weight loss of 1 to 2 pounds per week. There will be 24 weekly counseling meetings during the first 6 months, bi-weekly meetings between months 7 and 9, and monthly meetings between months 10 and 12.

Behavioral: Lifestyle Modification Counseling

Interventions

Vertical Sleeve Gastrectomy PROCEDURE

Surgical Procedure: Vertical Sleeve Gastrectomy

VSG + LSM

Lifestyle Modification Counseling BEHAVIORAL

Behavioral Intervention: Lifestyle Modification Counseling

LSM; VSG + LSM

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 30 to 70 years at eligibility visit.
• At least one of the following:
• Diagnosed with NASH with a total NAS ≥ 4 including a ballooning score of at least 1
• Diagnosed with T2DM or prediabetes, HbA1c\< 9%
• Body Mass Index (BMI): 35.0-60.0 kg/m2 at eligibility visit.
• Willingness to accept random assignment to either treatment group.
• Evidence of liver fat present in the baseline MR images
• Suitable for liver biopsy
• Willingness to comply with the follow-up protocol and successful completion of the run-in (described below).
• Written informed consent.
• English speaking

You may not qualify if:

• Cardiovascular event (myocardial infarction, acute coronary syndrome, coronary artery angioplasty or bypass, stroke) in the past six months.
• Current evidence of congestive heart failure, angina pectoris, or symptomatic peripheral vascular disease.
• Pulmonary embolus or thrombophlebitis in the past six months.
• Cancer of any kind (except basal cell skin cancer or cancer in situ) unless documented to be disease-free for five years.
• Significant anemia (hemoglobin 2.0 g/dL or more below normal range) or history of coagulopathy. (Low range for women would be 10, low range for men would be 11)
• Serum creatinine \>1.8 mg/dL.
• Serum total bilirubin greater than the upper limit of normal in the absence of Gilbert's syndrome, or alkaline phosphatase or ALT or AST greater than 2.5x the upper limit of normal. Elevated INR.
• Alcohol intake more than one drink or \>20 grams per day
• History of stomach surgery, bile duct surgery, pancreatic surgery, splenectomy, or colon resection.
• Gastric or duodenal ulcer in the past six months.
• History of intra-abdominal sepsis (except for uncomplicated appendicitis or diverticulitis more than six months prior to enrollment).
• Previous organ transplantation.
• Self-reported HIV-positive status, active tuberculosis, active malaria, chronic hepatitis B or C, cirrhosis, or inflammatory bowel disease.
• Currently pregnant or nursing, or planning to become pregnant in the next two years.
• History of alcohol, drug, or opioid dependency (excluding nicotine) in the past five years.

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (2)

University of San Fransisco

San Francisco, California, 94143, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

COMPLETED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Sayeed Ikramuddin, M.D., M.H.A.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon Jannatpour, MS

CONTACT

6126727422; sjannatp@umn.edu

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: July 3, 2018
• First Posted: July 16, 2018
• Study Start: July 1, 2021
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (2)