A Trial to Evaluate Safety, Feasibility and Efficacy of the ReCET Procedure (EMINENT-2)

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (ReCET system by the Endogenex with the Gen-2 catheter) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus.

Detailed Description
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The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (ReCET system by the Endogenex with the Gen-2 catheter) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus and an adequate beta cell reserve in a randomized sham-controlled study. The aimed effect is an adequate or improved glucose regulation without the need for insulin therapy. Secondary effects include improved cardiovascular, hepatic, and metabolic parameters.

Official Title
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Endoscopic Application of Pulsed Electric Fields Using by the Endogenex Generation 2 ReCET System for Duodenal Mucosal Regeneration for EliMination of INsulin in the treatmENT of Type 2 Diabetes: a Randomized Double-blind Sham Controlled Trial to Evaluate Safety, Feasibility and Efficacy Study

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Device: ReCET
* Drug: Semaglutide, 1.0 mg/mL
* Other: Sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes mellitus 28 - 75 years of age On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month BMI ≥ 24 and ≤ 42 kg/m2 HbA1c ≤ 64 mmol/mol (8.0%) Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml) Willing to comply with study requirements and able to understand and comply with signed informed consent Exclusion Criteria: Diagnosed with Type 1 Diabetes or with a history of ketoacidosis Current use of multiple daily doses insulin or insulin pump. Current or within the last 3 months use of a GLP-1 analogue. Known autoimmune disease, as evidenced by a positive Anti-GAD test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions History of chronic or acute pancreatitis Known active hepatitis or active liver disease Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) which cannot be discontinued for 3-5 days before and 48 hours after the procedure and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 48 hours before and 48 hours after the procedure in accordance with the local protocol Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 5 days before and 48 hours after the procedure in accordance with the local protocol. Use of aspirin is allowed. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications Anemia, defined as Hgb < 6.2 mmol/l Known history of severe permanent cardiac arrhythmia's with clinical symptoms Significant cardiovascular disease, including known history of valvular disease or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the screening visit With any implanted electronic devices or duodenal metallic implants eGFR or MDRD < 30 ml/min/1.73m^2 Active systemic infection Active malignancy within the last 5 years Not potential candidates for surgery or general anesthesia Active illicit substance abuse or alcoholism Pregnancy or wish getting pregnant in next year Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

Ages Eligible for Study
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Minimum Age: 28 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study is a single-center, double-blind, sham-controlled trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ReCET procedure<br>Patients receive ReCET (Re-Cellularization via Electroporation Therapy), which is performed using the ReCET device. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started. | Device: ReCET<br>* Investigational product.<br>Drug: Semaglutide, 1.0 mg/mL<br>* Already registered medicine for type 2 diabetes<br>|
| Sham Comparator: Sham procedure<br>Patients receive sham procedure, this consists of placing an Endogenex catheter, or a catheter with a similar circumference at the endoscopists discretion in the stomach and leaving it in place for 30 minutes. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started | Drug: Semaglutide, 1.0 mg/mL<br>* Already registered medicine for type 2 diabetes<br>Other: Sham procedure<br>* The sham control for the ReCET procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety] | The incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs 24 weeks post ReCET procedure. | 24 weeks | 
| Percentage of patients off insulin at 24 weeks [efficacy] | Percentage of patients free of insulin at 24 weeks post ReCET with an HbA1c ≤ 58 mmol/mol compared to sham. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary safety endpoint 1 - hypoglycemic events | Number of hypoglycemic events | Through study completion (1 to 1,5 year) | 
| Secondary safety endpoint 2 - SAEs | All SAEs | Through study completion (1 to 1,5 year) | 
| Secondary feasibility endpoint 1 - technical success rate | Technical success rate, defined as percentage of subjects successfully completed the ReCET procedure (defined as ≥ 3 ablations). | 24 weeks (after cross-over) | 
| Secondary feasibility endpoint 2 - GLP-1RA tolerability | Percentage of subjects adequately using and tolerating GLP-1RA (semaglutide). | Through study completion (1 to 1,5 year) | 
| Secondary efficay endpoint 1 - HbA1c 48 weeks | Protocol driven number of subjects free of insulin at 48 weeks, including an HbA1c ≤ 58 mmol/mol. | at 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Duodenal ablation, Endoscopy, Electroporation