Safety and Feasibility of a Novel Endoscopic Intervention for the Treatment of 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 an open-label study to assess the safety and feasibility of the DyaMX device for endoscopic duodenal mucosal regeneration in individuals with type 2 diabetes inadequately controlled on glucose-lowering medications.

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

Inclusion Criteria:

1. 18-70 years of age
2. Current diagnosis of T2D
3. History of T2D for less than or equal to 10 years, or use insulin for less or equal to 10 years
4. HbA1C of 7.5-11.0%
5. BMI 24-40 kg/m2
6. If treated with non-insulin glucose lowering mediations, the medications (1-4 medications) should be stable for at least 12 weeks prior to baseline visit. If treated with basal insulin, the daily insulin dose should be within 20-60 IU.
7. Agree not to donate blood during participation in the study.
8. If treated with non-insulin glucose lowering medications, participant should have weight stability (defined as a < 5% change in body weight) for at least 12 weeks prior to the screening visit
9. Able to comply with study requirements and understand and sign the Informed Consent Form
10. Women of childbearing potential must be using an acceptable method of contraception throughout the study
11. Willing and able to perform self-monitoring blood glucose and comply with study visits and study tasks as required per protocol.

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 for those on non-insulin medications.

5. Current use of multiple daily dose insulin or insulin pump

6. Hypoglycemia unawareness

7. History of ≥1 severe hypoglycemia (defined by needing for third-party assistance), unless a clear correctable precipitating factor can be identified, 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.

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 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 Phentermine, Meridia, Xenical, or over-the-counter weight loss medications (prescription medication)

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

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

26. Known history of cardiac arrhythmia

27. 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.

28. Estimated glomerular filtration rate (eGFR) ≤ 30 ml/min/1.73m2.

29. 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.

30. With any implanted electronic devices or duodenal metallic implants

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

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

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

34. Women breast feeding

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

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

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

    Additional exclusion criteria to be confirmed during the screening process:

38. HbA1c < 7.5% or > 11% at baseline visit

39. Any severe hypoglycemic event since the screening visit

40. Glucose level <54 mg/dl (3.0 mmol/l) in more than 1% of time by CGM since the screening visit

41. Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15 mmol/L) after an overnight fast or >360 mg/dl (>20 mmol/l) in a randomly performed measurement that is confirmed by a second measurement (not on the same day) since screening visit

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

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

44. Grade III or greater esophagitis on endoscopy

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

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

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

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