ESG vs GLP-1RA vs ESG + GLP-1RA in Patients With Obesity, NAFLD and Advanced Fibrosis: A Randomized Controlled Trial

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Endoscopic bariatric and metabolic therapies (EBMT) are a non-invasive, safe alternative treatment for patients with obesity. Current FDA- approved devices include intragastric balloons (IGB) and suturing devices for endoscopic sleeve gastroplasty (ESG). These gastric interventions work by interfering with how the stomach expands to accept and process a meal, which slows down how fast the stomach empties. ESG, the procedure the investigators are doing in this study, involves endoscopic suturing to reduce the length and width of the stomach so that the patient feels full faster. Semaglutide is a popular medication for weight loss, and has shown significant weight loss with a good safety profile in clinical trials.

In this study, the investigators will compare ESG, Semaglutide only, and an ESG + Semaglutide combination, on weight loss for subjects undergoing the procedure with a history of obesity, liver fibrosis and NAFLD. To better understand how these impact obesity and liver fibrosis, the investigators will track weight loss, laboratory values, liver stiffness, and the patients overall liver health.

The suturing device used in the ESG procedure and the semaglutide are all approved by the U.S. Food and Drug Administration (FDA) for endoscopic procedures in the upper gastrointestinal tract and medication management of obesity.

This is a study that will randomize patients to 1 of 3 different treatment options: ESG only, Semaglutide only or ESG + Semaglutide. The investigators want to see if adding the weight loss medication to the ESG procedure will increase weight loss and how it will impact liver health.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pichamol Jirapinyo, MD, MPH
• Treatments: Semaglutide

Criteria

Inclusion Criteria:

1. Age 21-65

2. BMI ≥ 30 and ≤40 kg/m²

3. Willingness to comply with the substantial lifelong dietary restrictions required by the treatment plan

4. History of failure with non-surgical weight-loss methods

5. Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, and completing diet counseling

6. Residing within a reasonable distance from the investigator's office and able to travel to the investigator to complete all routine follow- up visits

7. Ability to give informed consent

8. Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods

Exclusion Criteria:

1. History of foregut or gastrointestinal (GI) surgery (except uncomplicated cholecystectomy or appendectomy)

2. Prior gastrointestinal surgery with sequelae, i.e. obstruction, and/or adhesive peritonitis or known abdominal adhesions.

3. Prior open or laparoscopic bariatric surgery.

4. Prior surgery of any kind on the esophagus, stomach or any type of hiatal hernia surgery.

5. Any inflammatory disease of the gastrointestinal tract including severe (LA Grade C or D) esophagitis, Barrett's esophagus, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn's disease.

6. 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.

7. Gastrointestinal stromal tumors, history of premalignant gastric lesions (intestinal metaplasia), history of familial and nan-familial adenomatous syndromes.

8. A gastric mass or gastric polyps > 1 cm in size.

9. A hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or intractable gastro-esophageal reflux symptoms.

10. A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the endoscope.

11. Achalasia or any other severe esophageal motility disorder

12. Severe coagulopathy.

13. Insulin-dependent diabetes (either Type 1 or Type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or a HgbA1C≥9.

14. Subjects with any serious health condition unrelated to their weight that would increase the risk of endoscopy

15. Chronic abdominal pain

16. Motility disorders of the GI tract such as gross esophageal motility disorders, gastroparesis or intractable constipation

17. Hepatic insufficiency or cirrhosis

18. Use of an intragastric device prior to this study due to the increased thickness of the stomach wall preventing effective suturing.

19. Active, untreated psychological issues preventing participation in a life-style modification program

20. Patients unwilling to participate in an established medically-supervised diet and behavior modification program, with routine medical follow-up.

21. Patients receiving daily prescribed treatment with high dose aspirin (> 80mg daily), anti-inflammatory agents, anticoagulants or other gastric irritants.

22. Patients who are unable or unwilling to take prescribed proton pump inhibitor medication

23. Patients who are pregnant or breast-feeding.

24. Subjects with Severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, Myocardial infarction within the past 6 months, poorly-controlled hypertension, required use of NSAIDs

25. Subjects taking medications on specified hourly intervals that may be affected by changes to gastric emptying, such as anti-seizure or anti-arrhythmic medications

26. Subjects who are taking corticosteroids, immunosuppressants, and narcotics

27. Symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease.

28. Pre-existing respiratory disease such as moderate or severe chronic obstructive pulmonary disease (COPD) requiring steroids, pneumonia or cancer.

29. Diagnosis of autoimmune connective tissue disorder (e.g. lupus, erythematous, scleroderma) or immunocompromised.

30. Specific diagnosed genetic disorder such as Prader Willi syndrome.

31. Eating disorders including night eating syndrome (NES), bulimia, binge eating disorder, or compulsive overeating

32. Known history of endocrine disorders affecting weight such as uncontrolled hypothyroidism.