Safety and Feasibility of Novel Therapy for Duodenal Mucosal Regeneration for Type II Diabetes

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, open-label study to assess the feasibility and preliminary safety of the Endogenex Device for endoscopic duodenal mucosal regeneration in patients with type 2 Diabetes inadequately controlled on 2-3 non-insulin glucose-lowering medications.

Detailed Description
-----------------
Individuals who sign the informed consent will be screened for study eligibility. Eligible participants will be treated with the Endogenex procedure and followed up for 48 weeks.

Official Title
-----------------
Safety and Feasibility of Endoscopic Application of a Novel Therapy for Duodenal Mucosal Regeneration in the Treatment of Type II Diabetes

Conditions
-----------------
Diabetes, Diabetes Type 2, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Disease, Endocrine System Diseases, Diabetes Mellitus

Intervention / Treatment
-----------------
* Device: The Endogenex Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 22- 65 years of age Current diagnosis of T2D History of T2D for at least 3 years and less than or equal to 10 years HbA1C of 7.5-10.0%, inclusive BMI 24-40 kg/m2, inclusive On two to three non-insulin glucose lowering mediations, with one at maximum tolerated dose and another at half-maximum dose at least, with no changes in medication for at least 12 weeks prior to baseline visit prior to baseline visit History of failed attempt to reach glycemic goal by lifestyle modifications Weight stability (defined as a < 5% change in body weight) for at least 12 weeks prior to the screening visit Agree not to donate blood during participation in the study. Able to comply with study requirements and understand and sign the Informed Consent Form Women of childbearing potential must be using an acceptable method of contraception throughout the study Willing and able to use CGM for the duration of the study and comply with study visits and study tasks as required per protocol. Proof of COVID 19 vaccination. Exclusion Criteria: Diagnosed with type 1 diabetes History of diabetic ketoacidosis or hyperosmolar nonketotic coma Probable insulin production failure, defined as overnight fasting C-peptide serum <1 ng/mL (333pmol/l). Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes) in last 2 years. Current use of insulin Hypoglycemia unawareness History of ≥1 severe hypoglycemia episode (defined by needing for third-party assistance) in past 6 months from the screening visit Known autoimmune disease, as evidenced by a positive anti-glutamic acid decarboxylase (GAD) test, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder. (Participants with adequately controlled primary hypothyroidism may be included). Previous GI surgery that has changed GI anatomy or could limit treatment of the duodenum, such as Billroth 2, Roux-en-Y gastric bypass, gastric band or other similar procedures or conditions. Known history of a structural or functional disorder of the upper GI tract that may impede passage of the device through the upper GI tract or increase risk of tissue damage during an endoscopic procedure, including esophagitis, stricture/stenosis, varices, diverticula, or other disorder of the esophagus, stomach and duodenum. Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen) History of, or gastrointestinal symptoms suggestive of gastroparesis. Acute gastrointestinal illness in the previous 7 days Known history of irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease History of chronic or acute pancreatitis. Known active hepatitis or active liver disease other than NASH/NAFLD. Alcoholic liver disease, as indicated by ANI > 0 Current use of anticoagulation therapy (such as warfarin) that cannot be discontinued for 7 days before and 14 days after the procedure. Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 14 days before and 14 days after the procedure. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of acetaminophen and low dose aspirin is allowed. Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 12 weeks prior to the baseline visit. Use of drugs known to affect GI motility (e.g. Metoclopramide) Use of weight loss medications such as Meridia, Xenical, Phentermine or over-the-counter weight loss medications (prescription medication) Currently taking, or unable to stop taking dietary supplements or herbal agents, including vitamin C or multivitamins containing vitamin C at >500 mg per day, multivitamins containing biotin (vitamin B7), and supplements for hair, skin, and nail growth. Multivitamins not containing biotin are permitted. Persistent anemia, defined as hemoglobin <10 g/dL. Known history of hemoglobinopathy. Known history of blood donation or transfusion within 3 months prior to the Screening Visit. Known history of cardiac arrythmia 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. Estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73m2 (estimated by MDRD). Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the participant a poor candidate for clinical trial participation in the opinion of the investigator. History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside the normal range at screening) With any implanted electronic devices or duodenal metallic implants Not a candidate for upper GI endoscopy or general anesthesia. Active illicit substance abuse or alcoholism (>2 drinks/day regularly) Active malignancy within the last 5 years (excluding non-melanoma skin cancers) Women breastfeeding Participating in another ongoing clinical trial of an investigational drug or device. Any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation. Critically ill or has a life expectancy <3 years Additional exclusion criteria to be confirmed during the screening process: HbA1c < 7.5% or > 10% at baseline visit Any severe hypoglycemic event since the screening visit CGM readings <54 mg/dl in more than 1% of time by CGM since the screening visit CGM readings > 360 mg/dL in more than 1% of time Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic) Women of child-bearing potential with a positive urine pregnancy test at baseline visit LA Grade C or greater esophagitis on endoscopy Abnormalities of the GI tract preventing endoscopic access to the duodenum Anatomic abnormalities in the duodenum that would preclude the completion of the treatment procedure, including tortuous anatomy Endoscopic observation of upper gastrointestinal abnormality such as ulcers, polyps, varices, strictures, congenital or intestinal telangiectasia Any other anatomical or endoscopic abnormalities/characteristics that, in the opinion of the investigator, would preclude safe use of the investigational device or procedure

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional<br>All eligible patients will receive the endoscopic Endogenex procedure. | Device: The Endogenex Device<br>* The Endogenex device is designed to induce duodenal mucosal regeneration using pulsed electric field. The Endogenex procedure is a non-surgical, endoscopic procedure.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint | Portion of participants experiencing device- or procedure-related serious adverse events (SAE) | 12 weeks post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HbA1c | Mean changes from baseline in HbA1c | 4, 12, 24, 36, 48 weeks | 
| Changes in fasting plasma glucose | Mean changes from baseline in FPG | 4, 12, 24, 36, 48 weeks | 
| Changes in insulin resistance | Mean changes from baseline in HOMA-IR | 4, 12, 24, 36, 48 weeks | 
| Changes in post-prandial glucose | Mean changes in PPG by mixed meal tolerance test | 4, 12, 24, 36, 48 weeks | 
| Changes in Weight | Mean changes from baseline in weight | 4, 12, 24, 36, 48 weeks | 
| Changes systolic and diastolic blood pressure | Mean changes from baseline in systolic and diastolic blood pressure | 4, 12, 24, 36, 48 weeks | 
| Changes in alanine aminotransferase (ALT) | Mean changes from baseline in ALT | 4, 12, 24, 36, 48 weeks | 
| Changes in aspartate aminotransferase (AST) | Mean changes from baseline in AST | 4, 12, 24, 36, 48 weeks | 
| Changes in glucose-lowering medication usage | Changes in usage of glucose-lowering medications | 4, 12, 24, 36, 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endoscopy