DUODENAL RECELLULARIZATION VIA ELECTROPORATION IN POORLY CONTROLLED TYPE 2 DIABETES

Background
In the evolving treatment landscape for T2D, the duodenum, a key site for nutrient sensing and glucose metabolism regulation, presents a compelling target for new therapeutic approaches that seek to improve insulin sensitivity and glucose homeostasis. One promising technology involves the endoscopic application of pulsed electric fields to induce duodenal cell regeneration. Duodenal recellularization via electroporation (ReCET™, Endogenex Inc.) is a non-thermal, non-pharmacologic intervention that selectively targets mucosal and submucosal cells inducing irreversible electroporation that is followed by re-epithelialization of the duodenal surface with the intent of improving glucose metabolism. This first-in-human study evaluates the safety, feasibility and preliminary efficacy of ReCET in T2D patients inadequately controlled on glucose lowering medications.
Method
This is an ongoing multicenter, open-label, treatment-only study. Key eligibility criteria are 18-70 years of age, history of T2D for ≤10 years, HbA1c of 7.5%-11.0%, BMI of 24 – 40 kg/m2, C-peptide ≥ 333 pmol/l, and on 1-4 non-insulin GLMs. The primary endpoint is the incidence of device- or procedure-related serious adverse events (SAEs) at 12 wks. Secondary endpoints include technical success and changes in glycemic control at 24 wks. Patients are followed for 48 wks, with endoscopic follow up at 4 wks. The GLMs are maintained stable for ≥12 wks before and ≥24 wks after the procedure.
Results
Fifty-one patients have been enrolled and treated with two versions of catheters (Table 1). Technical success was 100%, with a mean treated length of 11.2 ± 2.7 cm, and median procedure time of 68 min (IQR 46 – 88). No device/procedure-related SAEs occurred. Incidence of device/procedure-related adverse events (AEs) were less frequent with the Gen 2 vs. Gen 1 device (10/21 vs 23/30, p<0.05). The most reported AEs were sore throat 49% (25/51) and transient diarrhea 22% (11/51). AEs were mild (76%) or moderate (24%) in severity. At 4 wks, the treated areas showed complete healing, were mostly unidentifiable endoscopically with no signs of stricture, ulceration, or other significant findings.
Glycemic control was significantly improved post-procedure from baseline with a trend towards greater effectiveness with double Tx and with the Gen 2 device (Figure 1). Mean change in HbA1c was -1.7% at 24 wks from baseline with the Gen 2 device. Follow up in the Gen 2 treated group is ongoing. In patients treated with the Gen 1 device, improvement in glycemic effect was maintained at 48 wks in the double Tx group.
Conclusions
Endoscopic therapy using the ReCET system is safe and has demonstrated a clinically meaningful improvement in glycemic control in T2D patients uncontrolled on medications in this feasibility study.