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

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

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.

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.

Inclusion Criteria:

1. 22- 65 years of age
2. Current diagnosis of T2D
3. History of T2D for at least 3 years and less than or equal to 10 years
4. HbA1C of 7.5-10.0%, inclusive
5. BMI 24-40 kg/m2, inclusive
6. 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
7. History of failed attempt to reach glycemic goal by lifestyle modifications
8. Weight stability (defined as a < 5% change in body weight) for at least 12 weeks prior to the screening visit
9. Agree not to donate blood during participation in the study.
10. Able to comply with study requirements and understand and sign the Informed Consent Form
11. Women of childbearing potential must be using an acceptable method of contraception throughout the study
12. Willing and able to use CGM for the duration of the study and comply with study visits and study tasks as required per protocol.
13. Proof of COVID 19 vaccination.

Exclusion Criteria:

1. Diagnosed with type 1 diabetes

2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma

3. Probable insulin production failure, defined as overnight fasting C-peptide serum <1 ng/mL (333pmol/l).

4. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes) in last 2 years.

5. Current use of insulin

6. Hypoglycemia unawareness

7. History of ≥1 severe hypoglycemia episode (defined by needing for third-party assistance) in past 6 months from the screening visit

8. 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).

9. 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.

10. 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.

11. Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen)

12. History of, or gastrointestinal symptoms suggestive of gastroparesis.

13. Acute gastrointestinal illness in the previous 7 days

14. Known history of irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease

15. History of chronic or acute pancreatitis.

16. Known active hepatitis or active liver disease other than NASH/NAFLD.

17. Alcoholic liver disease, as indicated by ANI > 0

18. Current use of anticoagulation therapy (such as warfarin) that cannot be discontinued for 7 days before and 14 days after the procedure.

19. Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 14 days before and 14 days after the procedure.

20. 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.

21. 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.

22. Use of drugs known to affect GI motility (e.g. Metoclopramide)

23. Use of weight loss medications such as Meridia, Xenical, Phentermine or over-the-counter weight loss medications (prescription medication)

24. 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.

25. Persistent anemia, defined as hemoglobin <10 g/dL.

26. Known history of hemoglobinopathy.

27. Known history of blood donation or transfusion within 3 months prior to the Screening Visit.

28. Known history of cardiac arrythmia

29. 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.

30. Estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73m2 (estimated by MDRD).

31. 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.

32. History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside the normal range at screening)

33. With any implanted electronic devices or duodenal metallic implants

34. Not a candidate for upper GI endoscopy or general anesthesia.

35. Active illicit substance abuse or alcoholism (>2 drinks/day regularly)

36. Active malignancy within the last 5 years (excluding non-melanoma skin cancers)

37. Women breastfeeding

38. Participating in another ongoing clinical trial of an investigational drug or device.

39. Any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation.

40. Critically ill or has a life expectancy <3 years

    Additional exclusion criteria to be confirmed during the screening process:

41. HbA1c < 7.5% or > 10% at baseline visit

42. Any severe hypoglycemic event since the screening visit

43. CGM readings <54 mg/dl in more than 1% of time by CGM since the screening visit

44. CGM readings > 360 mg/dL in more than 1% of time

45. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic)

46. Women of child-bearing potential with a positive urine pregnancy test at baseline visit

47. LA Grade C or greater esophagitis on endoscopy

48. Abnormalities of the GI tract preventing endoscopic access to the duodenum

49. Anatomic abnormalities in the duodenum that would preclude the completion of the treatment procedure, including tortuous anatomy

50. Endoscopic observation of upper gastrointestinal abnormality such as ulcers, polyps, varices, strictures, congenital or intestinal telangiectasia

51. Any other anatomical or endoscopic abnormalities/characteristics that, in the opinion of the investigator, would preclude safe use of the investigational device or procedure