Clinical trial NCT05984238: A Trial to Evaluate Safety, Feasibility and Efficacy of the ReCET Procedure (EMINENT-2)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: Type 2 Diabetes
Duodenal ablation
Endoscopy
Electroporation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Endogenex
First posted: 2023-08-09
Enrollment: 32
Sex: ALL
Minimum age (years): 28
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study is a single-center, double-blind, sham-controlled trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety]
timeFrame: 24 weeks
measure: Percentage of patients off insulin at 24 weeks [efficacy]
timeFrame: 24 weeks
Secondary outcomes:
measure: Secondary safety endpoint 1 - hypoglycemic events
timeFrame: Through study completion (1 to 1,5 year)
measure: Secondary safety endpoint 2 - SAEs
timeFrame: Through study completion (1 to 1,5 year)
measure: Secondary feasibility endpoint 1 - technical success rate
timeFrame: 24 weeks (after cross-over)
measure: Secondary feasibility endpoint 2 - GLP-1RA tolerability
timeFrame: Through study completion (1 to 1,5 year)
measure: Secondary efficay endpoint 1 - HbA1c 48 weeks
timeFrame: at 48 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: North-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Jacques JG Bergman, MD
role: PRINCIPAL_INVESTIGATOR
References: