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

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.

Eligibility

Inclusion Criteria:

* 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.
* All patients must have insurance with no exclusion for obesity related treatments or management of obesity surgery complications. This applies to all participants enrolled in the study
* 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

Exclusion Criteria:

* 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.
* Active psychosocial or psychiatric problem that is likely to interfere with adherence to the protocol.
* A score of 17 or greater on the CES-D questionnaire administered on a typical week for the participant.
* Presence of any chronic or debilitating disease that would make adherence to the protocol difficult.
* Serum c-peptide \<1.0 ng/ml post prandial.
* Exclusions may also be made at the discretion of the attending physician or the eligibility committee.
* History of endoscopy demonstrating esophagitis or Barrett's changes in the esophagus.
* Any history of dysphagia.
* Fibrosis score \> 3
* Use of Rezdiffra (resmetirom).

Conditions2

Locations2 sites

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