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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Device: ReCET; Drug: Semaglutide, 1.0 mg/mL; Other: Sham procedure

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Celine BE Busch, MD; Phone Number: +31621357593; Email: c.b.busch@amsterdamumc.nl
• Study Contact Backup: Name: Kim van den Hoek, MD; Phone Number: +31621357593; Email: k.vandenhoek@amsterdamumc.nl

Study Locations

• Netherlands
  • North-Holland
    • Amsterdam, North-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC
      • Contact: Celine BE Busch, MD; Phone Number: +31621357593; Email: diabetes-onderzoek@amsterdamumc.nl
      • Principal Investigator: Jacques JG Bergman, MD PhD
      • Sub-Investigator: Celine BE Busch, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with type 2 diabetes mellitus
2. 28 - 75 years of age
3. On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month
4. BMI ≥ 24 and ≤ 42 kg/m2
5. HbA1c ≤ 64 mmol/mol (8.0%)
6. Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml)
7. Willing to comply with study requirements and able to understand and comply with signed informed consent

Exclusion Criteria:

1. Diagnosed with Type 1 Diabetes or with a history of ketoacidosis
2. Current use of multiple daily doses insulin or insulin pump.
3. Current or within the last 3 months use of a GLP-1 analogue.
4. 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
5. 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
6. History of chronic or acute pancreatitis
7. Known active hepatitis or active liver disease
8. Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease
9. History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
10. 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
11. 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.
12. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase
13. Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide)
14. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
15. Anemia, defined as Hgb < 6.2 mmol/l
16. Known history of severe permanent cardiac arrhythmia's with clinical symptoms
17. 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
18. With any implanted electronic devices or duodenal metallic implants
19. eGFR or MDRD < 30 ml/min/1.73m^2
20. Active systemic infection
21. Active malignancy within the last 5 years
22. Not potential candidates for surgery or general anesthesia
23. Active illicit substance abuse or alcoholism
24. Pregnancy or wish getting pregnant in next year
25. Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study.
26. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ReCET procedure; 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; Investigational product.; Drug: Semaglutide, 1.0 mg/mL; Already registered medicine for type 2 diabetes
Sham Comparator: Sham procedure; 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; Already registered medicine for type 2 diabetes; Other: Sham procedure; The sham control for the ReCET procedure.

What is the study measuring?

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 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
Secondary safety endpoint 1 - hypoglycemic events	Number of hypoglycemic events	Through study completion (1 to 1,5 year)

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Endogenex
• Investigators: Principal Investigator: Jacques JG Bergman, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

Helpful Links

• Website for people that are interested in participating.

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Endoscopy; Electroporation; Duodenal ablation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NL83266.000.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes