Hepatic Energy Fluxes in NASH and NAS Patients

NCT03997422 | Active Not Recruiting DMC

• 1 other identifier: SURG-2019-27704
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Diseases along the nonalcoholic fatty liver disease spectrum, which are tightly coupled to the obesity epidemic, are soon to become the commonest indication for liver transplantation in the United States. Bariatric surgery shows great promise in the treatment of these diseases. The studies proposed herein will be the first to measure in humans the relationships among (i) the liver's ability to burn fat and make glucose, two of its primary functions; (ii) the severity of nonalcoholic fatty liver disease; and (iii) the responses to bariatric surgery. These experiments will support deeper future mechanistic investigations of the metabolic mechanisms underlying nonalcoholic steatohepatitis (NASH) improvement with bariatric surgery. The premise of this study is that deranged hepatic mitochondrial metabolism is a key biomarker and mediator of the nonalcoholic fatty liver disease (NAFLD)/NASH continuum, and the central hypothesis the investigators will test is that preoperative hepatic fat oxidation and glucose production flux parameters differ between low versus high NAFLD activity score (NAS), and response of the liver to bariatric surgery can be predicted by preoperative fluxes.

Conditions

NASH - Nonalcoholic Steatohepatitis; NAS; Overweight or Obesity; Weight Loss; Bariatric Surgery Candidate

Outcome Measures

Primary Outcomes (1)

• Hepatic Energy Fluxes

  Non-invasive dual isotope tracer-coupled magnetic resonance spectroscopy (MRS) will be used to measure tricarboxylic acid cycle (TCA) flux, anaplerosis, and gluconeogenesis. Outcome reported in micromols per minute per kg of lean body mass.

  12 months

Secondary Outcomes (1)

• Histologic improvements in NAFLD Activity Score (NAS)

  12 months

Study Arms (1)

Vertical Sleeve Gastrectomy (VSG)

EXPERIMENTAL

Bariatric surgical procedure

Procedure: Vertical Sleeve Gastrectomy (VSG)

Interventions

Vertical Sleeve Gastrectomy (VSG) PROCEDURE

Vertical Sleeve gastrectomy will be performed using five laparoscopic ports using a 40 French Bougie as a template. If a hiatal hernia is identified it will be repaired. This practice has greatly reduced postoperative reflux disease (see human subjects protection). As VSG for patients with a BMI 30.0-34.9 kg/m2 is not covered by insurance the University hospital will cover costs for up to 24 patients.

Vertical Sleeve Gastrectomy (VSG)

Eligibility Criteria

• Age: 40 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 67 years at eligible visit
• Diagnosed with NASH with a total NAS ≥ 3 including a ballooning score of at least 1, or non-NASH/NAFLD with a total NAS ≤3, or Diagnosed with T2DM or prediabetes, HbA1c\< 8% , or CAP score greater than or equal to 248 on Fibroscan
• Body Mass Index (BMI) 30.0-55.0 kg/m2 at eligibility visit
• Willingness to accept surgical intervention after an individual seminar session
• Expect to live or work within approximately three-hour traveling time from the study clinic for the duration of the one-year trial
• Willingness to comply with the follow-up protocol and successful completion of the run-in
• Written informed consent
• Suitable for liver biopsy using the percutaneous approach

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.
• Cardiac stress test indicating that surgery or IMM would not be safe.
• 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 1.0 g/dL or more below normal range) or history of coagulopathy.
• Serum creatinine \>1.5 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 2.5 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, or cirrhosis
• Currently pregnant or nursing, or planning to become pregnant in the next two years.

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Overweight; Obesity; Weight Loss

Condition Hierarchy (Ancestors)

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

Study Officials

• Sayeed Ikramuddin

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 21, 2019
• First Posted: June 25, 2019
• Study Start: July 1, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)