ENLIGHT Trial: ESG With Fundal Mucosal Ablation

Obesity is associated with a number of chronic health conditions, including type 2diabetes, 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 thevolume and length of the stomach and create a sleeve‐like configuration. The gastricfundus is generally preserved during ESG. Although ESG has been shown to produceclinically meaningful weight loss, weight loss following ESG is generally less than thatachieved with surgical sleeve gastrectomy.One possible explanation for this difference is the role of the gastric fundus inappetite regulation. The fundus contains a large number of cells that produce ghrelin, ahormone involved in hunger and food intake. Procedures that remove or alter the gastricfundus may reduce circulating ghrelin levels. Fundal mucosal ablation (FMA) is anemerging endoscopic technique designed to treat the mucosal lining of the gastric funduswhile preserving the stomach itself. Early studies have suggested that FMA may reducefasting ghrelin levels and may contribute to reductions in hunger and body weight. TheENLIGHT trial is designed to determine whether adding FMA to standard ESG providesadditional benefit compared with ESG alone.Participants assigned to the ESG group will undergo standard ESG under generalanesthesia. Participants assigned to the ESG with FMA group will undergo standard ESGtogether with FMA during the same procedure. Following the procedure, participants inboth groups will receive similar standard post‐procedure care. Participants will befollowed for approximately 52 weeks after the procedure.Study SignificanceThe ENLIGHT Trial is intended to provide comparative evidence regarding whether addingFMA to ESG improves weight loss while maintaining an acceptable safety and tolerabilityprofile. The study will also help determine whether the combined procedure has additionaleffects on metabolic health, obesity‐related conditions, patient‐reported outcomes, andfasting ghrelin levels.