Endoscopic application of pulsed electric fields by the DyaMX system® for duodenal Mucosal regeneration for elimination of INsulin in the treatmENT of type 2 diabetes: a first in human safety, feasibility and efficacy study

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1.Diagnosed with type 2 diabetes mellitus
2.28 -75 years of age
3.Treatment with long acting insulin = 10 years
4.On daily long acting insulin dose = 1 U/kg
5.No specific restrictions regarding concomitant other glucose lowering drugs
6.BMI = 24 and = 40 kg/m2
7.HbA1c = 8.0% (64 mmol/mol)
8.Fasting C-peptide = 0.5 nmol/L (1.5 ng/ml)
9.Fasting Plasma Glucose = 10 mmol/L
10.Willing to comply with study requirements and able to understand and comply with informed consent
11.Signed informed consent form

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.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
4.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
5.History of chronic or acute pancreatitis
6.Known active hepatitis or active liver disease
7.Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn’s Disease and Celiac Disease
8.History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
9.Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 7 days before and 14 days after the procedure
10.Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure. Use of aspirin is allowed.
11.Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase
12.Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide)
13.Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
14.Persistent Anemia, defined as Hgb < 6.2 mmol/l
15.Known history of cardiac arrythmia
16.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
17.With any implanted electronic devices or duodenal metallic implants
18.eGFR or MDRD < 30 ml/min/1.73m^2
19.Active systemic infection
20.Active malignancy within the last 5 years
21.Not potential candidates for surgery or general anesthesia
22.Active illicit substance abuse or alcoholism
23.Pregnancy or wish getting pregnant in next year
24.Participating in another ongoing clinical trial of an investigational drug or device
25.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>The safety endpoint is the incidence rate of the following events at 6 weeks, 6 months, and 12 months post-procedure: - All procedure and device-related Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) - All SAEs - Number of hypoglycemic events (self-measured blood glucose level of 3.1 mmol/L) or requiring 3rd party assistance)</p>

Secondary Outcome Measures

Name	Time	Method
<p>The following secondary endpoints are evaluated at baseline and during follow-up to identify improvement in cardiovascular, metabolic and hepatic parameters compared to baseline measurements: - HbA1c - Achieving target HbA1c = 7.0% - FPG - Time in range for glucose levels using CGM - Glucose variability as assessed by the CGM - Blood pressure and central hemodynamics via Nexfin device - HOMA-IR - Weight - Waist-hip ratio - Lipids - Liver fat content (only at 6 and 12 months) via Fibroscan/PDFF - Urine micro albumin - DTSQs (diabetes treatment satisfactory questionnaire) and DTSQc. DTSQc (change” version to overcome ceiling effect) only at 6 and 12 months.</p>