Effect of Endoscopic Sleeve Gastroplasty in Patients With Obesity and MASH: A Randomized Controlled Trial

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.

Eligibility

Inclusion Criteria:

1. Age ≥ 18 (male or female)
2. BMI ≥30 kg/m2
3. Self-reported stable weight (no weight change \>5%) for 6 months prior to the first study visit
4. Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory/imaging/additional tests, and completing diet counseling
5. Willingness to NOT start a new anti-obesity medication for the following 12 months
6. Residing within a reasonable distance from the investigator's office and able to travel to the investigator to complete routine follow-up visits
7. Ability to give informed consent
8. Women of childbearing potential (i.e., not post-menopausal, nor surgically sterilized) must agree to use adequate birth control methods

Exclusion Criteria:

1. Known history of other chronic liver diseases (viral hepatitis, autoimmune hepatitis, drug-induced hepatitis, and genetic)
2. Treatment with vitamin E (at doses ≥800 IU/day), pioglitazone, obeticholic acid, or resmetirom \<90 days before the first study visit
3. History of foregut or gastrointestinal (GI) surgery (except uncomplicated fundoplication, cholecystectomy or appendectomy)
4. Prior bariatric surgery
5. Prior endoscopic sleeve gastroplasty
6. Any inflammatory disease of the GI tract, including severe (LA Grade C or D) esophagitis, Barrett's esophagus with dysplasia, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn's disease
7. Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses
8. Severe gastroesophageal reflux disease (GERD)
9. A structural abnormality in the esophagus or pharynx, such as a stricture or diverticulum, that could impede passage of the endoscope.
10. Achalasia or any other severe esophageal motility disorder
11. Chronic abdominal pain
12. Gastroparesis or intractable constipation
13. Hepatic insufficiency or cirrhosis
14. Severe coagulopathy
15. Insulin-dependent diabetes (either type 1 or type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or HgbA1C ≥ 10%
16. Patients on an anti-platelet agent, anticoagulant agent or chronic/routine use of NSAIDs
17. Patients on corticosteroids, immunosuppressants, or narcotics
18. Patients on an anti-seizure or anti-arrhythmic medication
19. Patients who are pregnant or breastfeeding
20. Excessive alcohol consumption (\>20 g per day for women; \>30 g per day for men)
21. Active smoking
22. History of poorly controlled hypertension, coronary artery disease, congestive heart failure, cardiac arrhythmia
23. History of respiratory diseases such as chronic obstructive pulmonary disease (COPD) requiring steroids, pneumonia, or cancer
24. History of autoimmune connective tissue disorder such as lupus, scleroderma or immunocompromised disease
25. History of active malignancy
26. History of genetic or hormonal causes for obesity, such as Prader Willi syndrome
27. History of endocrine disorders affecting weight, such as uncontrolled hypothyroidism
28. Eating disorders, including night eating syndrome, bulimia, binge eating disorder or compulsive overeating
29. Active psychological issues preventing participation in a lifestyle modification program as determined by a psychologist

Conditions20

Locations2 sites

Browse More Trials