VSG + Lifestyle Changes for Fatty Liver Disease

Overseen By Allison Wolf

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

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: 3

Duration: 12 months

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two approaches for treating fatty liver disease: lifestyle changes alone or lifestyle changes combined with Vertical Sleeve Gastrectomy (VSG). The main goal is to determine which method more effectively reduces liver issues over 12 months. The trial seeks participants with fatty liver disease, possibly accompanied by type 2 diabetes or prediabetes, and a body mass index (BMI) between 35 and 60. Participants must be willing to follow a diet and exercise plan and may also need to undergo surgery. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could shape future treatments for fatty liver disease.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that vertical sleeve gastrectomy (VSG) is generally safe for people with obesity. Research indicates that VSG can significantly improve liver issues like scarring and fat buildup in about 60% of patients. This surgery is also associated with lower risks of major heart problems and death. However, the safety of weight-loss surgery, such as VSG, for people with liver disease remains not fully understood. Most reports focus on the first 30 days after surgery, so researchers continue to study long-term safety. For those considering participation in a trial involving VSG, this data suggests it is generally well-tolerated. It is always best to discuss the risks and benefits with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Vertical Sleeve Gastrectomy (VSG) with Lifestyle Modification Counseling for treating fatty liver disease because this approach targets weight loss in two powerful ways. VSG involves surgically reducing stomach size, leading to rapid weight loss without strict calorie limits initially, which is a fresh take compared to standard lifestyle changes alone. Meanwhile, the Lifestyle Modification Counseling offers a structured plan to change eating and exercise habits, modeled after the successful LookAHEAD trial. This dual strategy not only promotes significant weight loss but also aims to improve liver health more effectively than current treatments that rely solely on diet and exercise adjustments.

What evidence suggests that this trial's treatments could be effective for fatty liver disease?

Research has shown that Vertical Sleeve Gastrectomy (VSG), one of the treatments in this trial, can effectively treat fatty liver disease. Studies have found that VSG can reduce liver fat and improve liver health for many individuals. In one study, most patients experienced reduced fat buildup and inflammation in the liver, with 30% also seeing reduced liver scarring. Additionally, previous trials, such as the LookAHEAD study, demonstrated that weight loss through diet and exercise, part of the Lifestyle Modification Counseling arm in this trial, can enhance liver health by decreasing fat and inflammation. Both VSG and lifestyle changes, as separate treatment arms in this trial, have shown promising results for improving fatty liver disease. ^{6 7 8 9 10}

Who Is on the Research Team?

Sayeed Ikramuddin, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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

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

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lifestyle Modification Counseling
• Vertical Sleeve Gastrectomy

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

In a study involving 54 Sprague-Dawley rats, vertical sleeve gastrectomy (VSG) combined with a diet change resulted in significant weight loss, particularly in rats that switched from a high-fat diet to a standard chow diet after surgery.

The combination of VSG and dietary changes not only led to major reductions in body weight but also normalized adipose tissue weight, indicating a comprehensive improvement in body composition over the 12-week study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet Change After Sleeve Gastrectomy Is More Effective for Weight Loss Than Surgery Only. Rossell, J., González, M., Mestres, N., 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]

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]

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