880-P: Effects of Energy Dosing on Safety and Efficacy in an Open-Label Study of Endoscopic Pulsed Electric Field Induced Electroporation in Type 2 Diabetes (REGENT-1 Trial)

Introduction and Objective: The ReCET™ System (endoscopic Re-Cellularization via Electroporation Therapy) uses pulsed electric field (PEF), to induce duodenal mucosal apoptotic-like cell death followed by regeneration. We evaluated the intervention energy dose on metabolic outcomes. Methods: REGENT-1 studied PEF therapy at three doses in T2D adults on 1-4 non-insulin agents. Group 1) Gen 1 catheter 600V, single treatment (n=12); Group 2) Gen 1 catheter, 600V, double treatment (n=18); and Group 3) Gen 2 catheter (increased treated surface area [TSA]), double treatment 750V (n=21). Primary endpoint: Serious adverse events (SAEs). Secondary endpoints included metabolic changes at 24 and 48 weeks. Results: One intervention related SAE occurred in 51 participants (age 52.9±7.9 years, BMI 31.4±3.5 kg/m², baseline HbA1c 8.7±0.9%[72±9mmol/mol]). Other device/procedure-related adverse events (76 events in 47/51 participants) were mild and transient. Increased PEF dose (two applications, and higher voltage plus larger catheter diameter) correlated with metabolic improvements at 24 and 48 weeks. (Table 1) Conclusion: PEF-induced duodenal regeneration with the ReCET System resulted in improved metabolic outcomes that were dose-dependent. These promising findings suggest that further research is warranted. Disclosure D.N. O'Neal: None. A. Sartoretto: Research Support; Endogenex. Advisory Panel; Bariatek. Research Support; Erbe Elektromedizin GmbH. Consultant; Boston Scientific Corporation. Speaker's Bureau; Menarini. S. Chandran: None. R. Vaughan: None. B. Holt: None. A.J. Thompson: Other Relationship; Endogenex. G. Cameron: None. B. AbuDayyeh: Other Relationship; Endogenex. Consultant; Boston Scientific Corporation, Metronics, Olympus. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. C.H. Sorli: Employee; Endogenex. E.I. Ekinci: Research Support; Amgen Inc, Novo Nordisk, Lilly Diabetes, AstraZeneca, Endogenex, Versanis. Advisory Panel; Lilly Diabetes, Novo Nordisk.