A Trial to Evaluate Safety, Feasibility and Efficacy of Endoscopic Duodenal PEF Therapy

The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (with the Endogenex System en Gen 2 Device) 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.

Inclusion criteria

• Diagnosed with type 2 diabetes mellitus
• 28 - 75 years of age
• On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month
• BMI ≥ 24 and ≤ 42 kg/m2
• HbA1c ≤ 64 mmol/mol (8.0%)
• Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml)
• Willing to comply with study requirements and able to understand and comply with signed informed consent

Exclusion criteria

• Diagnosed with Type 1 Diabetes or with a history of ketoacidosis
• Current use of multiple daily doses insulin or insulin pump.
• Current or within the last 3 months use of a GLP-1 analogue.
• 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
• 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
• History of chronic or acute pancreatitis
• Known active hepatitis or active liver disease
• Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease
• History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
• 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
• 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.
• Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase
• Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide)
• Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
• Anemia, defined as Hgb < 6.2 mmol/l
• Known history of severe permanent cardiac arrhythmia's with clinical symptoms
• 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
• With any implanted electronic devices or duodenal metallic implants
• eGFR or MDRD < 30 ml/min/1.73m^2
• Active systemic infection
• Active malignancy within the last 5 years
• Not potential candidates for surgery or general anesthesia
• Active illicit substance abuse or alcoholism
• Pregnancy or wish getting pregnant in next year
• Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study.
• Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation