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

Not Applicable

Recruiting

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

• Registration Number: NCT05984238
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

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

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 Timeline

• Study First Submitted: 2023-07-11
• Study First Submitted QC: 2023-08-02
• Study Start: 2023-08-03
• Study First Posted: 2023-08-09
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-18
• Last Update Posted: 2023-09-21
• Primary Completion: 2025-01
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ReCET procedure	ReCET	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.
ReCET procedure	Semaglutide, 1.0 mg/mL	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.
Sham procedure	Semaglutide, 1.0 mg/mL	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
Sham procedure	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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam, North-Holland, Netherlands