Endoscopic application of pulsed electric fields using 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

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

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
4. BMI >= 24 and <= 40 kg/m2
5. HbA1c <= 8.0% (64 mmol/mol)
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 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: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Safety: Incidence rate of adverse events.<br /><br>• Feasibility: Procedure time and technical success rate<br /><br>• Primary efficacy: Protocol driven free of insulin at 6 months and HbA1c <= 7.5<br /><br>% in the active group, compared to the control group</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Secondary efficacy:<br /><br>- Time in range (flash glucose monitoring),<br /><br>- liver fat fraction (MRI-PDFF) and fibrosis<br /><br>- sympathovagal activity (Nexfin device).<br /><br>- bloodL HbA1c, HOMA-IR, Fasting Plasma Glucose<br /><br>- Weight, BMI, waist circumference<br /><br>- lipid panel, liverenzymes etc.<br /><br>- micro albumin<br /><br>- glucoregulatory hormones (Mixed Meal Test)<br /><br>- Microbiota diversity oral and fecal<br /><br>- Intake registration<br /><br><br /><br>In the active group, compared to the control group at 6 months</p><br>