ENLIGHT Trial: ESG With Fundal Mucosal Ablation

Obesity is associated with a number of chronic health conditions, including type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, obstructive sleep apnea, and metabolic liver disease. Treatment options include lifestyle modification, anti-obesity medications, bariatric surgery, and endoscopic weight-loss procedures. ESG is an endoscopic procedure in which full-thickness sutures are placed to reduce the volume and length of the stomach and create a sleeve-like configuration. The gastric fundus is generally preserved during ESG. Although ESG has been shown to produce clinically meaningful weight loss, weight loss following ESG is generally less than that achieved with surgical sleeve gastrectomy. One possible explanation for this difference is the role of the gastric fundus in appetite regulation. The fundus contains a large number of cells that produce ghrelin, a hormone involved in hunger and food intake. Procedures that remove or alter the gastric fundus may reduce circulating ghrelin levels. Fundal mucosal ablation (FMA) is an emerging endoscopic technique designed to treat the mucosal lining of the gastric fundus while preserving the stomach itself. Early studies have suggested that FMA may reduce fasting ghrelin levels and may contribute to reductions in hunger and body weight. The ENLIGHT trial is designed to determine whether adding FMA to standard ESG provides additional benefit compared with ESG alone. Participants assigned to the ESG group will undergo standard ESG under general anesthesia. Participants assigned to the ESG with FMA group will undergo standard ESG together with FMA during the same procedure. Following the procedure, participants in both groups will receive similar standard post-procedure care. Participants will be followed for approximately 52 weeks after the procedure. Study Significance The ENLIGHT Trial is intended to provide comparative evidence regarding whether adding FMA to ESG improves weight loss while maintaining an acceptable safety and tolerability profile. The study will also help determine whether the combined procedure has additional effects on metabolic health, obesity-related conditions, patient-reported outcomes, and fasting ghrelin levels.