Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes

1. Diagnosed with Type 1 Diabetes (T1D)

2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma

3. Probable insulin production failure, defined as 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)

5. Current use of injectable medications for diabetes (insulin, GLP-1RA)

6. Current use of glyburide, a sulfonylurea (SU) glucose-lowering drug for diabetes

7. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year)

8. Known autoimmune disease, 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 could limit treatment of the duodenum such as Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions

10. History of chronic or acute pancreatitis

11. History of diabetic gastroparesis

12. Known active hepatitis or active liver disease

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

15. Known history of a structural or functional disorder of the esophagus that may impede passage of the device through the gastrointestinal tract or increase risk of esophageal damage during an endoscopic procedure, including Barrett's esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, esophageal diverticula, esophageal perforation, or any other disorder of the esophagus

16. Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug refractory esophageal reflux symptoms

17. Known history of a structural or functional disorder of the stomach including gastroparesis, gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (\> 2 cm), cancer or any other disorder of the stomach

18. Known history of chronic symptoms suggestive of a structural or functional disorder of the stomach, including any symptoms of chronic upper abdominal pain, chronic nausea, chronic vomiting, chronic dyspepsia or symptoms suggestive of gastroparesis, including post-prandial fullness or pain, post-prandial nausea or vomiting or early satiety

19. Known history of duodenal ulcer, intestinal diverticula (diverticulitis), intestinal varices, intestinal stricture/stenosis, small bowel obstruction, or any other obstructive disorder of the GI tract

20. Currently have ongoing symptoms suggestive of intermittent small bowel obstruction, such as recurrent bouts of post-prandial abdominal pain, nausea or vomiting

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

22. History of coagulopathy, upper gastrointestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia

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

24. Current use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure.

25. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of low dose aspirin is allowed.

26. Current use of serotonergic medications (SSRI)

27. Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit

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

29. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications

30. Untreated/inadequately treated hypothyroidism, defined as an elevated Thyroid-Stimulating Hormone (TSH) level at Screening; if on thyroid hormone replacement therapy, must be on stable dose for at least 6 weeks prior to Screening

31. Persistent Anemia, defined as Hemoglobin \<10 g/dL

32. Subjects who have donated blood or received a transfusion in the prior 3 months

33. Subjects with conditions that alter red blood cell turnover

34. Subjects with prosthetic joints

35. Significant cardiovascular disease including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack or stroke within the last 6 months

36. Moderate or severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) \<45 ml/min/1.73m2 (estimated by MDRD)

37. 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 subject a poor candidate for clinical trial participation in the opinion of the Investigator

38. Active systemic infection

39. Active malignancy within the last 5 years (with the exception of treated basal cell or treated squamous cell carcinoma)

40. Subjects with a personal or family history of medullary thyroid carcinoma

41. Subjects with Multiple Endocrine Neoplasia syndrome type 2

42. Not a candidate for surgery or general anesthesia

43. Active illicit substance abuse or alcoholism

44. Current smoker

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

46. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

47. Unwilling or unable to perform SMBG, complete the patient diary, or comply with study visits and other study procedures as required per protocol

1. A1c post Run-In Phase \< 7.5% (59 mmol/mol) or \> 9.5% (86 mmol/mol)

2. Any severe hypoglycemic event, defined as hypoglycemia requiring third-party assistance; or any clinically significant hypoglycemic event, defined as self-monitored or laboratory plasma glucose level \< 54 mg/dL (3.0 mmol/L); or ≥ 2 glucose alert values ≤70 mg/dL (3.9 mmol/L), unless a clear correctable precipitating factor can be identified, since the screening visit (Visit 1)

3. 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 during Medication Run-In Period and confirmed by a second measurement (not on the same day)

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

5. WOCBP with a positive urine pregnancy test at Baseline Visit

6. Active and uncontrolled GERD defined as grade III esophagitis or greater

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

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

9. Malignancy newly diagnosed by endoscopy

10. Upper gastrointestinal conditions such as ulcers, polyps, varices, strictures, congenital or acquired intestinal telangiectasia

Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes

What this study is about

Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes

What this study is about