A Trial to Evaluate Safety, Feasibility and Efficacy of Endoscopic Duodenal PEF Therapy (EMINENT-2)

Endoscopic Application of Pulsed Electric Fields Using the Endogenex Generation 2 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 (with the Endogenex System en Gen 2 Device) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide, 1.0 mg/mL; Device: PEF therapy using the Endogenex Device; 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 (with the Endogenex System en Gen 2 Device) 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 (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam UMC

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
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 PEF therapy procedure.
Active Comparator: PEF therapy procedure; Patients receive endoscopic duodenal PEF therapy, which is performed using the Endogenex device. 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; Device: PEF therapy using the Endogenex Device; Investigational product.

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 PEF therapy procedure.	24 weeks
Percentage of patients off insulin at 24 weeks [efficacy]	Percentage of patients free of insulin at 24 weeks post PEF therapy 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 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)
Secondary feasibility endpoint 1 - technical success rate	Technical success rate, defined as percentage of subjects successfully completed the PEF therapy procedure (defined as ≥ 3 ablations).	24 weeks (after cross-over)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Busch CBE, van den Hoek K, Neefjes-Borst EA, Nieuwdorp M, van Baar ACG, Bergman JJHGM. Optimizing duodenal tissue acquisition for mechanistic studies of duodenal ablation in type 2 diabetes. Endosc Int Open. 2025 Jan 29;13:a25032135. doi: 10.1055/a-2503-2135. eCollection 2025.
• Musso G, Pinach S, Saba F, De Michieli F, Cassader M, Gambino R. Endoscopic duodenal mucosa ablation techniques for diabetes and nonalcoholic fatty liver disease: A systematic review. Med. 2024 Jul 12;5(7):735-758.e2. doi: 10.1016/j.medj.2024.03.014. Epub 2024 Apr 4.

Helpful Links

• Website for people that are interested in participating.

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2023
• Primary Completion (Actual): March 21, 2025
• Study Completion (Actual): May 28, 2026

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): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Endoscopy; Electroporation; Duodenal ablation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; semaglutide
• 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