Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes, Duodenal ablation, Endoscopy, Electroporation
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.
Interventions
DEVICEReCET
Investigational product.
Already registered medicine for type 2 diabetes
OTHERSham procedure
The sham control for the ReCET procedure.
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Endogenex
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
In this study, both the study team and the study subjects are blinded to the treatment through the 24 week follow-up visit. While the endoscopist is not blinded to individual treatments, he or she is blinded to cohort level data and is not responsible for patient follow-up. At the 24 week visit, the subject and study team are unblinded. The subjects who received the sham treatment undergo ReCET.
Intervention model description
This study is a single-center, double-blind, sham-controlled trial.
Eligibility
Sex/Gender
ALL
Age
28 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 safety endpoint 1 - hypoglycemic events | Through study completion (1 to 1,5 year) | Number of hypoglycemic events |
| 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. |
| 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 safety endpoint 2 - SAEs | Through study completion (1 to 1,5 year) | All SAEs |
Countries
Netherlands
Outcome results
None listed