Bariatric Surgery for Fatty Liver Disease

Overseen By Allison Wolf

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Amiodarone, Methotrexate, Glucocorticoids, others

Disqualifiers: Cardiovascular events, Cancer, Alcohol, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 week

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications associated with nonalcoholic fatty liver disease, such as amiodarone, methotrexate, and oral glucocorticoids, for more than 4 weeks within the last 2 months before screening. You also need to stop taking pioglitazone or high-dose vitamin E within the last 2 months before screening.

Is vertical sleeve gastrectomy (VSG) generally safe for humans?

Vertical sleeve gastrectomy (VSG) is generally considered safe, but there are some risks of complications like bleeding and leaks. It may also affect bone health, especially in adolescents and young adults. ^{1 2 3 4 5}

How does the treatment Vertical Sleeve Gastrectomy (VSG) differ from other treatments for fatty liver disease?

Vertical Sleeve Gastrectomy (VSG) is unique because it can improve liver health independently of weight loss, unlike other treatments that primarily focus on weight reduction. This surgical procedure reduces the size of the stomach, which can lead to changes in eating behavior and metabolism, offering a novel approach to treating fatty liver disease. ^{2 3 6 7 8}

What data supports the effectiveness of the treatment Vertical Sleeve Gastrectomy (VSG) for fatty liver disease?

Research shows that after sleeve gastrectomy, there is an improvement or even complete resolution of nonalcoholic fatty liver disease (NAFLD) in morbidly obese patients, as indicated by changes in liver health markers. ^{2 3 6 9 10}

Who Is on the Research Team?

Sayeed Ikramuddin, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults aged 18-67 with a BMI of 30.0-55.0 kg/m2, diagnosed with NASH (NAS ≥3) or non-NASH/NAFLD (NAS ≤3), and possibly T2DM or prediabetes are eligible for this trial focused on liver health in relation to obesity. Participants must consent to surgery, live near the clinic for follow-ups, have insurance covering obesity treatments, and be suitable for liver biopsy.

Inclusion Criteria

Expect to live or work within approximately three-hour traveling time from the study clinic for the duration of the one-year trial

Your body mass index (BMI) is between 30 and 55.

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

Exclusion Criteria

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.

I have not taken specific medications that could cause fatty liver disease in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Assessment

Baseline measurements of hepatic energy fluxes using MRS and preoperative liver biopsies for NAS score determination

4 weeks

1 visit (in-person)

Treatment

Participants undergo Vertical Sleeve Gastrectomy (VSG) as a bariatric surgical procedure

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in hepatic energy fluxes and NAS score post-surgery

12 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Vertical Sleeve Gastrectomy (VSG)

Trial Overview The study is testing how Vertical Sleeve Gastrectomy (VSG), a type of bariatric surgery, affects liver function—specifically fat burning and glucose production—in patients with varying severities of fatty liver disease related to obesity.

How Is the Trial Designed?

Group I: Vertical Sleeve Gastrectomy (VSG) Experimental Treatment 1 Intervention

Bariatric surgical procedure

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

In a study of 200 patients, laparoscopic vertical sleeve gastrectomy (VSG) was found to have a shorter operative time and hospital stay compared to single-stage laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS).

However, while VSG is technically simpler and has promising outcomes, BPD/DS resulted in significantly greater excess weight loss at 6 months post-surgery, indicating it may be more effective for long-term weight management in morbidly obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of vertical sleeve gastrectomy versus biliopancreatic diversion. Sucandy, I., Titano, J., Bonanni, F., et al.[2021]

In a 2-year study of 66 adolescents and young adults undergoing vertical sleeve gastrectomy (VSG), patients experienced significant weight loss of 25.3%, but also a concerning 8.5% decline in total hip bone mineral density (BMD), indicating potential negative effects on bone health.

The study found that VSG led to a decrease in volumetric BMD at the distal radius and tibia, primarily due to loss of trabecular bone, which may increase the risk of skeletal fragility in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study. Mitchell, DM., Singhal, V., Animashaun, A., et al.[2023]

After 5 years post-vertical sleeve gastrectomy (VSG), patients maintained significant weight loss, with a mean body mass index (BMI) reduction from 46.2 kg/m2 to 32.9 kg/m2, indicating the procedure's long-term efficacy in obesity management.

The surgery led to substantial improvements in obesity-related conditions, with 63% of patients experiencing remission of type 2 diabetes and 60% for hypertension at 5 years, although there was an increase in gastroesophageal reflux disease (GERD) cases over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Outcomes After Vertical Sleeve Gastrectomy for Severe Obesity: A Prospective Cohort Study. Flølo, TN., Andersen, JR., Kolotkin, RL., et al.[2018]

In a study of over 513,000 patients who underwent vertical sleeve gastrectomy (VSG), staple-line reinforcement (SLR) methods like buttressing (BR) and oversewing (OS) were found to significantly reduce the rates of overall and major bleeding compared to no reinforcement (NR), although they resulted in longer operative times and hospital stays.

No SLR method significantly reduced the incidence of leaks, but bleeding was linked to a higher occurrence of leaks and increased morbidity and mortality, suggesting that using SLR techniques could improve patient outcomes after VSG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database. Aboueisha, MA., Freeman, M., Allotey, JK., et al.[2023]

Vertical sleeve gastrectomy (VSG) led to significant weight loss in adolescents with obesity, with body weight decreasing from an average of 136.6 kg to 87.4 kg over 52 weeks (P < .001).

After VSG, adolescents showed a reduced willingness to exert effort for high-calorie candies, indicating a decreased reward value for these foods, which may contribute to long-term weight loss and maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vertical sleeve gastrectomy in adolescents reduces the appetitive reward value of a sweet and fatty reinforcer in a progressive ratio task. Abdeen, GN., Miras, AD., Alqahtani, AR., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Reversal of NAFLD After VSG Is Independent of Weight-Loss but RYGB Offers More Efficacy When Maintained on a High-Fat Diet. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis : A Randomized Controlled Trial. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Comparison of vertical sleeve gastrectomy versus biliopancreatic diversion. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Improvement of nonalcoholic fatty liver disease in morbidly obese patients after sleeve gastrectomy: association of ultrasonographic findings with lipid profile and liver enzymes. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Five-Year Outcomes After Vertical Sleeve Gastrectomy for Severe Obesity: A Prospective Cohort Study. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Robotic-assisted vertical sleeve gastrectomy in adolescents: Do BMI limits apply? [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Vertical sleeve gastrectomy in adolescents reduces the appetitive reward value of a sweet and fatty reinforcer in a progressive ratio task. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Sleeve gastrectomy causes weight-loss independent improvements in hepatic steatosis. [2023]