Effect of Endoscopic Sleeve Gastroplasty in Patients With Obesity and MASH: A Randomized Controlled Trial
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver DiseaseInsulin ResistanceLiver DiseasesMetabolic Dysfunction-Associated SteatohepatitisObesityLiver FatMASHInsulin SensitivityInsulin Sensitivity/ResistanceDiabetes Mellitus, Type 2
- Interventions
- Device: ESG + lifestyle modificationBehavioral: Lifestyle modification
- Registration Number
- NCT06138821
- Lead Sponsor
- Pichamol Jirapinyo, MD, MPH
- Brief Summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery.
Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown.
In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.
- Detailed Description
The National Institutes of Health, the World Health Organization, and numerous other scientific organizations including the America Medical Association (AMA) recognize obesity as a chronic disease requiring primary therapy. Almost half of United States (U.S.) adults have obesity. The increasing prevalence of obesity in the U.S. has been accompanied by an increasing prevalence in its associated comorbid conditions including hypertension, diabetes, dyslipidemia, coronary heart disease, stroke, sleep apnea, osteoarthritis, and metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). The economic consequences of MASH are enormous, with the lifetime cost of care for all patients with MASH projected to be approximately $222 billion as of 2017.
Current treatment options for patients with MASLD/MASH are limited to lifestyle modification and the more recent Food and Drug Administration (FDA)-approved medication called resmetirom. Nevertheless, less than 10% of patients who undergo lifestyle modification experience at least 10% total weight loss (TWL), the threshold required for fibrosis regression. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery.
Over the past decades, endoscopic bariatric and metabolic therapies (EBMTs) have been developed to fill the treatment gap for obesity and MASLD/MASH. Specifically, compared to lifestyle modification, EBMTs are associated with greater weight loss with a higher proportion of patients reaching the 10% TWL threshold. Additionally, given its non-surgical, minimally-invasive nature, the safety profile for EBMTs appears more favorable compared to bariatric surgery. To date, there are two EBMT devices and/or procedures that are approved or cleared by the FDA. These include intragastric balloons (IGBs) and endoscopic sleeve gastroplasty (ESG).
The ESG procedure is an endoscopic minimally-invasive weight loss procedure where a commercially available, FDA-approved, full-thickness endoscopic suturing device (Overstitch; Boston Scientific, Marlborough, MA) is used to reduce the stomach volume by 70% through the creation of a restrictive endoscopic sleeve. This is accomplished by a series of endoluminally placed full-thickness sutures through the gastric wall, extending from the distal gastric body to the proximal gastric body. The investigators currently perform this procedure as a standard of care at Brigham and Women's Hospital (BWH). Our previous studies have demonstrated that ESG not only leads to significant weight loss, but also improves non-invasive tests (NITs) of liver steatosis and fibrosis, as well as MASH histologic features in patients with obesity and concomitant MASH. Nevertheless, it remains unclear if ESG is superior to lifestyle modification alone.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 18 years or older
- Obesity with a body mass index of 30-50 kg/m2
- A diagnosis of MASH with stage 1 (F1), 2 (F2), or 3 (F3) fibrosis (on a scale of 0 [no fibrosis] to 4 [cirrhosis]). MASH is defined as the nonalcoholic fatty liver disease activity score (NAS) of 4 or higher, with a score of 1 or higher for each subcomponent: steatosis, hepatocyte ballooning and lobular inflammation). Grading and staging of biopsies for the purposes of enrollment are done by a liver pathologist at the site of enrollment.
- cirrhosis
- excessive alcohol consumption (>20 g per day for women; >30 g per day for men)
- active smoking
- active malignancy
- being on an anticoagulant or anti-platelet medication
- being on a glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter-2 (SGLT2) inhibitor of any dose
- being initiated on an anti-obesity medication within 6 months prior to study enrollment or 12 months after study enrollment
- history of bariatric surgery or bariatric endoscopy
- changes in weight by greater than 5% within 6 months of study enrollment
- hemoglobin A1c (HbA1c) ≥10%
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ESG + lifestyle modification Lifestyle modification Endoscopic sleeve gastroplasty weight loss procedure with a lifestyle modification program for 12 months. ESG + lifestyle modification ESG + lifestyle modification Endoscopic sleeve gastroplasty weight loss procedure with a lifestyle modification program for 12 months. Lifestyle modification Lifestyle modification Lifestyle modification program for 12 months.
- Primary Outcome Measures
Name Time Method MASH resolution without worsening of liver fibrosis at 12 months Baseline, 12 months Comparison of endoscopic ultrasound (EUS)-guided liver biopsy results to assess MASH resolution at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
- Secondary Outcome Measures
Name Time Method Change in quality of life at 12 months Baseline, 6 and 12 months Compare changes in quality of life assessed using chronic liver disease questionnaire at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group
Change in eating behaviors at 12 months Baseline, 6 and 12 months Compare changes in eating behaviors evaluated using the Three Factor Eating Questionnaire (TFEQ) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver fibrosis using ELF score at 12 months Baseline, 12 months Comparison of ELF at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver fibrosis using FIB-4 at 12 months Baseline, 12 months Comparison of Fibrosis-4 (FIB-4) score at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver fat content using VCTE CAP score at 12 months Baseline, 12 months Comparison of liver fat content measured by controlled attenuation parameter (CAP) score on vibration-controlled transient elastography (VCTE) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver stiffness on MRE at 12 months Baseline, 12 months Comparison of liver stiffness measurement on magnetic resonance elastography (MRE) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver fat content using MRI-PDFF at 12 months Baseline, 12 months Comparison of liver fat content using MRI proton density fat fraction (MRI-PDFF) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
An improvement of liver fibrosis by at least one stage without worsening of MASH at 12 months Baseline, 12 months Comparison of endoscopic ultrasound (EUS)-guided liver biopsy results to assess an improvement of liver fibrosis at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver stiffness on VCTE at 12 months Baseline, 12 months Comparison of liver stiffness measurement on vibration-controlled transient elastography (VCTE) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in liver fibrosis using NFS at 12 months Baseline, 12 months Comparison of NAFLD fibrosis score (NFS) at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Percent total weight loss (%TWL) at 12 months Baseline, 1, 3, 6 and 12 months Comparison of weight loss at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compared to LM alone group.
Change in insulin resistance at 12 months Baseline, 12 months. Compare changes in insulin resistance using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Hemoglobin (HbA1c) values at 12 months compared to baseline in the ESG + lifestyle modification (LM) group compraed to LM alone group. groups
Safety parameters post-procedure Procedure day, 1, 3, 6, 9 and 12 months Rate of serious adverse events, defined as those classified as grade III-V according to the Clavien-Dindo classification in the ESG + LM group and LM alone group.
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States