Metabolic Surgery for Non-Alcoholic Fatty Liver Disease
(FLAMES Trial)
Recruiting in Palo Alto (17 mi)
+21 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Ali Aminian
Must not be taking: Semaglutide, Tirzepatide, Liraglutide, others
Disqualifiers: Chronic liver diseases, Type 1 diabetes, HIV, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment.
Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop all current medications, but you cannot have taken certain medications like semaglutide, tirzepatide, or liraglutide within 90 days before the study. If you have type 2 diabetes, you should have been on a stable dose of your anti-diabetic medication for at least 3 months before joining.
What data supports the effectiveness of this treatment for non-alcoholic fatty liver disease?
Research shows that bariatric surgery, a type of weight loss surgery, can significantly improve or even resolve non-alcoholic fatty liver disease (NAFLD) by helping with weight loss and improving insulin resistance (how the body uses insulin). This suggests that metabolic surgery is an effective treatment for NAFLD.
12345Is bariatric surgery safe for treating non-alcoholic fatty liver disease?
Bariatric surgery, which is a type of weight loss surgery, is generally considered safe for people with non-alcoholic fatty liver disease (NAFLD), although there may be a higher risk of complications in patients with liver cirrhosis. It's important for patients to discuss potential risks with their doctors before surgery.
678910How does metabolic surgery differ from other treatments for non-alcoholic fatty liver disease?
Metabolic surgery, also known as bariatric surgery, is unique because it not only helps with weight loss but also directly improves insulin resistance and reduces inflammation, which can significantly improve or even resolve non-alcoholic fatty liver disease, including severe cases.
1251112Eligibility Criteria
This trial is for individuals with MASLD, a liver condition linked to obesity and diabetes. It's open to those who have evidence of liver fibrosis (stages F1-F4). Participants must consent to a liver biopsy if they haven't had one recently.Inclusion Criteria
Has a negative urine pregnancy test at the first and at the randomization visits for women of childbearing potential
Self-reported stable weight in 3 months before the first study visit (no weight change >5% within 3 months prior to the first study visit)
I am between 18 and 70 years old.
+9 more
Exclusion Criteria
Anemia defined as hemoglobin less than 9 g/dL
Previous participation in this trial and got randomized to one of the study groups but did not proceed
Platelet count <100,000
+54 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline Assessment
Participants undergo baseline liver biopsy and other assessments
1-2 weeks
1 visit (in-person)
Treatment
Participants are randomized to either metabolic surgery or incretin-based therapies for 2 years
104 weeks
Regular visits as per treatment protocol
Follow-up
Participants are monitored for safety and effectiveness after treatment, including a repeat liver biopsy
4 weeks
2 visits (in-person)
Participant Groups
The study compares metabolic surgery against medical treatments using incretin-based therapies for MASH. About 120 patients will be randomly assigned to either the surgery or medication group and tracked over two years, including repeat liver biopsies.
2Treatment groups
Active Control
Group I: Metabolic SurgeryActive Control1 Intervention
FLAMES will examine the class effect (not the specific procedure effect) of metabolic surgery. The study is not intended to compare Roux-en-Y Gastric Bypass (RYGB) vs Sleeve Gastrectomy (SG) head-to-head. RYGB and SG constitute one group as a metabolic surgery group. Assignment of RYGB or SG is not based on a randomized design. Each patient and surgical team will make a shared decision about the most appropriate surgical procedure.
Group II: Incretin-Based TherapyActive Control1 Intervention
Three incretin-based medications that have been approved for treatment of obesity including liraglutide, semaglutide, or tirzepatide will be used in the nonsurgical group. The FLAMES will examine the class effect (not the specific drug effect) of incretin-based therapies. The study is not intended to compare semaglutide vs tirzepatide vs liraglutide head-to-head.
Metabolic Surgery is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Metabolic Surgery for:
- Metabolic Dysfunction-Associated Steatohepatitis (MASH)
- Non-Alcoholic Fatty Liver Disease (NAFLD)
- Liver Fibrosis
🇺🇸 Approved in United States as Metabolic Surgery for:
- Metabolic Dysfunction-Associated Steatohepatitis (MASH)
- Non-Alcoholic Fatty Liver Disease (NAFLD)
- Liver Fibrosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Banner Health CenterPhoenix, AZ
Indiana UniversityIndianapolis, IN
Mayo ClinicRochester, MN
Cleveland ClinicCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Ali AminianLead Sponsor
References
Bariatric Surgery and Metabolic Dysfunction-Associated Fatty Liver Disease: a 2022 Update. [2023]Non-alcoholic fatty liver disease (NAFLD) has been recently termed metabolic dysfunction-associated fatty liver disease (MAFLD) to address the strong association with the metabolic syndrome. The prevalence of MAFLD is significantly increased in obese individuals and treatment of obesity is currently the cornerstone of management of MAFLD. Bariatric and metabolic surgery nowadays emerges as a key therapeutic strategy for the treatment of the MAFLD. This review aims to provide an update on the novel studies reporting the outcomes of bariatric surgery on the spectrum of MAFLD, from hepatic steatosis to cirrhosis.
The Effects of Metabolic Surgery on Fatty Liver Disease and Nonalcoholic Steatohepatitis. [2022]Nonalcoholic fatty liver disease (NAFLD) is an under-recognized but increasingly important manifestation of the metabolic syndrome. Bariatric surgery, both through direct weight loss and more indirect effects on insulin resistance and improvements in inflammatory proteins, can have a profound effect on NAFLD, resulting in improvement or resolution of even high-grade liver disease.
Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. [2023]Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial.
Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery. [2022]It remains unclear to what extent and which components of advanced liver disease improve after bariatric surgery. We herein describe the histological outcome in patients with advanced NASH and its relationship with weight loss and metabolic improvement.
Bariatric Surgery as an Efficient Treatment for Non-Alcoholic Fatty Liver Disease in a Prospective Study with 1-Year Follow-up : BariScan Study. [2019]Bariatric surgery gains attention as a potential treatment for non-alcoholic fatty liver disease (NAFLD). The present study aimed to evaluate improvement of NAFLD after the two most common bariatric procedures with validated non-invasive instruments.
A Specifically Tailored Multistrain Probiotic and Micronutrient Mixture Affects Nonalcoholic Fatty Liver Disease-Related Markers in Patients with Obesity after Mini Gastric Bypass Surgery. [2023]Nonalcoholic fatty liver disease (NAFLD) is frequent among patients undergoing bariatric surgery. Beyond weight reduction, dietary supplements like micronutrients or probiotics that modify insulin resistance and lipotoxicity can be used to prevent or delay the progression of liver disease.
The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery. [2022]Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities.
Nonalcoholic fatty liver disease does not predict worse perioperative outcomes in bariatric surgery. [2020]Nonalcoholic fatty liver disease (NAFLD) occurs in 84-95% of obese individuals. Bariatric surgery (BS) is an effective treatment of obesity, with a potential sustained weight loss of 21-45%. The safety and efficacy of BS among NAFLD patients is not well established. The aim of this study was to determine outcomes for patients with NAFLD undergoing BS compared to patients without.
Increased plasma genistein after bariatric surgery could promote remission of NAFLD in patients with obesity. [2023]Bariatric surgery is associated with a positive effect on the progress of non-alcoholic associated fatty liver disease (NAFLD). Although weight loss is the obvious mechanism, there are also weight-independent mechanisms.
A Systematic Review of Bariatric Surgery in Patients with Liver Cirrhosis. [2018]Nonalcoholic steatohepatitis is becoming a common cause of liver cirrhosis and a significant number of patients undergoing bariatric surgery suffer with it. There is currently lack of consensus among surgeons regarding safety of bariatric surgery in patients with liver cirrhosis and the best bariatric procedure in these patients. This review investigates published English language scientific literature systematically in an attempt to answer these questions. Eleven studies that reported experience of bariatric surgery in cirrhotic obese patients were included in this review. This review shows an acceptably higher overall risk of complications and perioperative mortality with bariatric surgery in cirrhotic patients. Surgeons must discuss the possibility of an unexpected intraoperative diagnosis of cirrhosis preoperatively with all bariatric surgery patients and agree on a course of action.
The Effect of Bariatric Surgery on the Spectrum of Fatty Liver Disease. [2018]Nonalcoholic fatty liver disease is becoming one of the most common causes of liver disease in the western world. The most significant risk factors are obesity and the metabolic syndrome for which bariatric surgery has been shown to be an effective treatment. However, the effects of bariatric surgery on nonalcoholic fatty liver disease, specifically liver fibrosis and cirrhosis, are not well established. We review published bariatric surgery outcomes with respect to nonalcoholic liver disease. On the basis of this review we suggest that bariatric surgery may provide a viable treatment option for the treatment of nonalcoholic fatty liver disease, including patients with fibrosis and compensated cirrhosis, and that this topic should be a target of future investigation.
Bariatric Surgery and Non-Alcoholic Fatty Liver Disease: a Systematic Review of Liver Biochemistry and Histology. [2022]Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of global liver disease that is associated with the rising prevalence of obesity worldwide. There is now increasing clinical and mechanistic evidence reporting on the metabolic and weight loss effects of bariatric surgery on improving NAFLD in obese patients.