RESET System Pivotal Trial (Rev F)

A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the RESET System for Glycemic Improvement in Patients with Inadequately Controlled Type 2 Diabetes and Obesity, the STEP-1 Study.

A multi-center, double-blinded, randomized, sham-controlled trial to evaluate the safety and effectiveness of the RESET System plus moderate intensity lifestyle and dietary counseling compliant with 2024 ADA Standard of Care as compared to a sham control receiving moderate intensity lifestyle and dietary counseling. Both the treatment and sham group will practice medical management compliant with STEP-1 Study Guidelines. Patients will be randomized 3 (RESET):1 (Sham).

The objective of this study is to evaluate the safety and effectiveness of the RESET System when used with moderate intensity lifestyle and dietary counseling and medical management, in patients with baseline HbA1c ≥ 7.5% and ≤10%, and BMI ≥ 30 kg/m2 and ≤ 50kg/m2, whose diabetes medications consist of at least dual therapy for 3 months, yet have not achieved adequate HbA1c control (\<7%).

Specific objectives of this study are:

1. To determine if the RESET System significantly improves glycemic control
2. To determine that the RESET System can be safely used to improve glycemic control

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥22 years and ≤ 65 years
2. Have understood and signed the approved informed consent form
3. Diagnosis of type 2 diabetes
4. HbA1c ≥ 7.5% and ≤10%
5. BMI ≥30kg/m2 and ≤ 50kg/m2
6. Willing and able to comply with study requirements
7. Documented negative pregnancy test in women of childbearing potential
8. Women of childbearing potential not intending to become pregnant (continue to be on an approved form of birth control) for the duration of their trial participation, including post explant period. Women of child-bearing age without known sterilization will be placed on 1 form of birth-control to prevent unwanted pregnancies
9. At least one year of medical records available, including detailed medical therapy and dosing information
10. Failed to achieve adequate HbA1c reduction (\<7.5%) after dual therapy for at least 3-month stable dosage of diabetes medication(s), including insulin, metformin, SGLT-2 inhibitor, GLP-1 RA, Dual GLP-1/GIPR agonist or, other medications including meglitinides, sulfonylureas, thiazolidinediones, or DPP-4s.

Exclusion Criteria:

1. Previous treatment with the RESET System
2. Previous GI surgery that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner, or abnormal GI anatomical finding that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner
3. Hypoglycemia and/or DKA/HHNK in the last 6 months requiring 3rd party assistance
4. Known history of liver disease (e.g., viral or autoimmune etiology, METAVIR grade 2 or higher fibrosis/cirrhosis from a biopsy within the past 6 months, but not including incidental fatty liver)
5. eGFR of less than 45 ml/min/1.73 m2
6. Prior history of an abscess requiring hospitalization, intravenous antibiotics or drainage
7. Previous treatment for severe liver disease and/or biliary tract disease, including but not limited to, surgery, bile duct dilatation, and stent placement
8. Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis
9. Fasting C-peptide \< 1.0 ng/mL
10. Triglyceride level \> 600 mg/dL
11. Vitamin D deficiency (\<20ng/ml)
12. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy
13. Height \< 5 feet (152.4 cm)
14. Current alcohol addiction, current drug addiction or usage, of drugs such as, narcotics, opiates, or benzodiazepines and other addictive tranquilizers
15. History of pancreatitis, including gallstone related pancreatitis (subsequent to which patient has cholecystectomy)
16. Diagnosis of osteopenia or osteoporosis or currently taking denosumab, romosozumab-aqqg, bisphosphonates or teriparatide
17. Diagnosis of autoimmune connective tissue disorder (e.g. lupus erythematosus, scleroderma)
18. Active or recent (less than 12 months) gastroesophageal reflux disease (GERD) unless treated with H2RAs not PPI.
19. Uncontrolled thyroid disease, including a history of thyroid cancer, hyperthyroidism, or taking thyroid hormone for any reason other than primary hypothyroidism (TSH level must be between 0.4-4)
20. Currently taking prescription antithrombotic therapy (e.g. anticoagulant or antiplatelet agent) within 10 days prior to randomization and/or there is a need or expected need to use during the trial 9 months post implant procedure
21. Currently taking the following medications (within 30 days prior to randomization) and/or there is a need or expected need to use these medications during the trial 12 months post index procedure:

    Restricted Medications/Supplements Systemic corticosteroids Proton Pump Inhibitor (PPI) Drugs known to affect GI motility (e.g.metoclopramide) Prescription or over-the-counter weight loss medication(s) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), aspirin, ibuprofen, and other anti-inflammatory medication for study duration Medications known to cause significant weight gain or weight loss (e.g. chemotherapeutics)

    Supplements that are known or suspected to increase bleeding risk including but not limited to:

    Gingko biloba Ginseng Vitamins C \& E Turmeric St. John's wort Evening primrose oil Feverfew Green Tea Extract
22. Active H. pylori
23. History of Crohn's disease, atresias or untreated stenoses
24. Abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or upper gastrointestinal bleeding conditions within 3 months of randomization
25. Patients may be disqualified for study inclusion for any condition determined by the PI that places the patient at undue risk
26. Poor dentition not allowing complete chewing of food
27. Enrolled in another investigational study within 3 months of screening for this study (enrollment in observational studies is permitted)
28. Residing in a location without ready access to study site medical resources
29. Documented weight loss of 5% total body weight (TBW) anytime during the 3 months preceding randomization
30. Positive Fecal Immunochemical Test (FIT) at time of screening
31. History or observation of psychological disorder or behavior which could preclude compliance to the treatment and follow up plan
32. No access to an active telephone and internet service for provision of Follow Up Schedule calls and electronic diary
33. Having donated blood or received a blood transfusion in the 90 days prior to baseline labs. Patients should agree not to donate blood during the study
34. Any condition that increases red cell turnover, such as thalassemia
35. Existence of (\>5 cm string test) Pseudomonas aeruginosa, Stenotrophomonas maltophilia and/or Klebsiella pneumoniae serotype K1 and K2
36. A known sensitivity to nickel or titanium
37. Do not meet the screening criteria for MRI (i.e., MRI unsafe, or MRI conditional but not appropriate for the region of interest)
38. Patients with history or suspicion of coronary artery disease