Gastric fundal mucosal ablation followed by endoscopic sleeve gastroplasty in adults with obesity: a first-in-human two-phase pilot clinical trial

Background and Study Aims: Endoscopic sleeve gastroplasty (ESG) facilitates 13.6-16.2% total body weight loss (TBWL) at 12 months but falls short of surgical vertical sleeve gastrectomy (VSG), in part due to retention of the gastric fundus. In adults with obesity, gastric fundal mucosal ablation (GFMA) has reduced fasting plasma ghrelin (FPG), hunger, cravings, and accommodation. Combined GFMA-ESG could improve TBWL. This study aims to evaluate the effectiveness and safety of sequential GFMA followed by ESG in adults with obesity, building on previously published 6-month results of GFMA alone. Materials and Methods: This was a prospective, first-in-human, two-phase clinical trial. Ten participants underwent GFMA, followed by ESG at month six, and were followed for 12 months post-ESG (18 months total). GFMA was performed using hybrid argon plasma coagulation to lift-and-ablate the entire gastric fundal mucosa. ESG was performed using standard full-thickness endoscopic suturing of the gastric body. The primary endpoint was TBWL. Secondary endpoints were safety and change in FPG, maximum tolerated volume (MTV), and validated appetite questionnaires. Results: TBWL was 22.5 ± 8.3% at month 18. Hunger-related behaviors and eating self-efficacy showed sustained improvements. FPG decreased at month 6 and returned toward baseline by month 18, while MTV remained suppressed. No serious adverse events occurred. Conclusions: Sequential GFMA-ESG is safe and induces substantial weight loss, reduced MTV of ingested nutrients, and improved behavioral measures. This combination approach builds on prior traditional ESG and GFMA-only results and may represent a promising advancement of endoscopic therapeutic options for weight loss.

Publikationsverlauf

Eingereicht: 14. Januar 2026

Angenommen nach Revision: 26. Februar 2026

Accepted Manuscript online:
27. Februar 2026