VSG + Lifestyle Changes for Fatty Liver Disease

Recruiting in Palo Alto (17 mi)

Overseen by Sayeed Ikramuddin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Minnesota

Disqualifiers: Cardiovascular events, Cancer, Alcohol, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment VSG + Lifestyle Changes for Fatty Liver Disease?

Research shows that vertical sleeve gastrectomy (VSG) can lead to long-term weight loss and improve metabolic complications, which may help treat non-alcoholic fatty liver disease (NAFLD). Additionally, lifestyle changes like diet and exercise are recommended as first-line interventions for managing NAFLD. ^{1 2 3 4 5}

Is the combination of VSG and lifestyle changes safe for treating fatty liver disease?

The research highlights lifestyle changes like diet and exercise as safe first-line treatments for fatty liver disease. While specific safety data for combining these with Vertical Sleeve Gastrectomy (VSG) isn't detailed, VSG is a common surgical procedure generally considered safe for weight loss in obese patients. ^{5 6 7 8 9}

How does the VSG + Lifestyle Changes treatment for fatty liver disease differ from other treatments?

The VSG + Lifestyle Changes treatment is unique because it combines vertical sleeve gastrectomy (a type of weight-loss surgery) with lifestyle modifications like diet and exercise, which together can effectively reduce weight and improve metabolic health, potentially offering more comprehensive benefits for fatty liver disease compared to lifestyle changes alone. ^{1 7 10 11 12}

Research Team

Sayeed Ikramuddin, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults aged 30-70 with a BMI of 35.0-50.0 kg/m2, diagnosed with NASH (a type of liver disease) or prediabetes/T2DM, and an HbA1c level below 9%. Participants must consent to random treatment assignment, have insurance covering obesity treatments, live within two hours of the clinic, and be suitable for a liver biopsy.

Inclusion Criteria

I am between 30 and 70 years old.

I have NASH with a specific severity score, or I have type 2 diabetes or prediabetes with controlled HbA1c.

Body Mass Index (BMI): 35.0-50.0 kg/m2 at eligibility visit

Exclusion Criteria

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

I have had an organ transplant.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants are randomized to either Lifestyle Modification or Vertical Sleeve Gastrectomy with Lifestyle Modification, followed for 12 months

12 months

Regular visits at 1 week, 4 weeks, 12 weeks, 6 months, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Lifestyle Modification Counseling (Behavioral Intervention)
• Vertical Sleeve Gastrectomy (Procedure)

Trial Overview The study compares lifestyle modification alone versus vertical sleeve gastrectomy (VSG) combined with lifestyle changes over 12 months to see which better reduces liver damage in NASH patients. It aims to recruit and retain participants for invasive/non-invasive measurements and assess the safety of VSG.

Participant Groups

Group I: VSG + LSM Experimental Treatment 2 Interventions

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.

Group II: LSM Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

Findings from Research

In a study involving 35 Wistar rats with diet-induced non-alcoholic fatty liver disease (NAFLD), sleeve gastrectomy (SG) was found to be more effective than a very-low calorie diet (VLCD) in improving liver histology and reducing insulin resistance.

SG led to significant weight loss and decreased cardiovascular risk by lowering insulin resistance, leptin, total cholesterol, and triglyceride levels, while both SG and VLCD improved liver histology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease. Talavera-Urquijo, E., Rodríguez-Navarro, S., Beisani, M., et al.[2018]

Sleeve gastrectomy (SG) significantly reduced the effects of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice, improving glucose metabolism and decreasing fat accumulation in the liver.

The mechanism behind SG's effectiveness involves increasing hepatic NAD+ levels and upregulating the NRK1/NAD+/SIRT1 pathway, which are linked to improved lipid metabolism and reduced inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice. Hua, R., Wang, GZ., Shen, QW., et al.[2021]

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]

Nonalcoholic fatty liver disease (NAFLD) affects over 25% of the global population and is a major cause of chronic liver disease, leading to serious health issues like cirrhosis and liver cancer.

Lifestyle modifications, particularly weight loss, are essential first-line interventions for managing NAFLD, and the paper provides evidence-based recommendations for effective lifestyle changes in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. Younossi, ZM., Corey, KE., Lim, JK.[2021]

There is a growing need for better care pathways for patients at risk of advanced stages of non-alcoholic fatty liver disease (NAFLD), particularly in distinguishing between progressive fibrotic NAFLD and simple steatosis.

Implementing interdisciplinary care approaches will improve patient identification for necessary surveillance and treatment, while also enhancing understanding of NAFLD's relationship with lifestyle, genetics, and related health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Referral care paths for non-alcoholic fatty liver disease-Gearing up for an ever more prevalent and severe liver disease. van Dijk, AM., Schattenberg, JM., Holleboom, AG., et al.[2022]

A qualitative study involving 27 patients with nonalcoholic fatty liver disease (NAFLD) identified 19 barriers and 16 facilitators to weight management, highlighting that lack of time, energy, and awareness of NAFLD were significant obstacles.

Key facilitators for successful weight loss included having basic knowledge and skills about weight loss, strong motivation, and positive feedback from small successes, suggesting that education and support are crucial for improving weight management in NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM-B model of behaviour. Gu, Y., Zhou, R., Kong, T., et al.[2023]

The review analyzed seven trials involving 373 participants to assess the effects of weight reduction strategies, including lifestyle changes and the drug orlistat, on non-alcoholic fatty liver disease (NAFLD), but found insufficient data to draw strong conclusions due to high risk of bias.

There is a need for more rigorous randomized clinical trials with low risk of bias to better understand the benefits and harms of weight reduction in NAFLD patients, particularly regarding long-term outcomes like fibrosis and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight reduction for non-alcoholic fatty liver disease. Peng, L., Wang, J., Li, F.[2021]

Nonalcoholic fatty liver disease (NAFLD) can progress from a benign state (NAFL) to a more severe condition (NASH) that increases the risk of serious liver complications, highlighting the importance of early intervention.

Lifestyle changes, particularly weight loss of 5% to over 10%, are crucial for managing NAFLD, and for patients who struggle to achieve this, FDA-approved anti-obesity medications may be considered to help prevent disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When to Initiate Weight Loss Medications in the NAFLD Population. Yoo, ER., Sallam, S., Perumpail, BJ., et al.[2020]

Non-obese non-alcoholic fatty liver disease (NAFLD) is a common but often overlooked condition linked to metabolic disorders, highlighting the need for increased awareness among patients and healthcare professionals.

Lifestyle interventions, including improved diet and increased physical activity, have been shown to effectively reduce the risk and severity of non-obese NAFLD, suggesting that promoting these changes could significantly benefit affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease. Zhang, XL., Wang, TY., Targher, G., et al.[2022]

References

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

Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice. [2021]

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

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

4. 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]

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

AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Referral care paths for non-alcoholic fatty liver disease-Gearing up for an ever more prevalent and severe liver disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM-B model of behaviour. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Weight reduction for non-alcoholic fatty liver disease. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

When to Initiate Weight Loss Medications in the NAFLD Population. [2020]

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

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

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease. [2022]

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

Diet Change After Sleeve Gastrectomy Is More Effective for Weight Loss Than Surgery Only. [2018]