EndoBarrier System Pivotal Trial(Rev E v2)

Overview

A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the EndoBarrier 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 EndoBarrier System plus moderate intensity lifestyle and dietary counseling compliant with 2019 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 (EndoBarrier):1 (Sham).

Description

The objective of this study is to evaluate the safety and effectiveness of the EndoBarrier System when used with moderate intensity lifestyle and dietary counseling and medical management, in patients with baseline HbA1c ≥ 8.0% and ≤10%, and BMI ≥ 30 kg/m2 and ≤ 50kg/m2, whose diabetes medications consist of at least dual therapy for 3 months, excluding insulin, yet have not achieved adequate HbA1c control (<7%).

Specific objectives of this study are:

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

Eligibility

Inclusion Criteria:

1. Age ≥30 years and ≤ 65 years
2. Have understood and signed the approved informed consent form
3. Diagnosis of type 2 diabetes for ≤ 15 years
4. HbA1c ≥ 8.0% 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 2 forms 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 (<8%) after dual therapy for at least 3-month stable dosage of diabetes medication(s), including metformin, SGLT-2 inhibitor, GLP-1 RA or, other medications including meglitinides, sulfonylureas, thiazolidinediones, or DPP-4s. Use of insulin is an exclusion criterion. Patients should be at 70% of maximum dosage of diabetes medications or highest tolerable dosage.

Exclusion Criteria:

1. Previous treatment with the EndoBarrier System
2. Previous GI surgery that could preclude the ability to place the EndoBarrier Liner or affect the function of the EndoBarrier Liner, or abnormal GI anatomical finding that could preclude the ability to place the EndoBarrier Liner or affect the function of the EndoBarrier Liner
3. 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)
4. eGFR of less than 45 ml/min/1.73 m2
5. Prior history of an abscess requiring hospitalization, intravenous antibiotics or drainage
6. Previous treatment for severe liver disease and/or biliary tract disease, including but not limited to, surgery, bile duct dilatation, and stent placement
7. Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis
8. Fasting C-peptide < 1.0 ng/mL
9. Triglyceride level > 600 mg/dL
10. Vitamin D deficiency (<20ng/ml)
11. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy
12. Height < 5 feet (152.4 cm)
13. Current or past alcohol addiction, current or past drug addiction, or current drug usage, of drugs such as, narcotics, opiates, or benzodiazepines and other addictive tranquilizers
14. History of pancreatitis, including gallstone related pancreatitis (subsequent to which patient has cholecystectomy)
15. Diagnosis of osteopenia or osteoporosis or currently taking denosumab, romosozumab-aqqg, bisphosphonates or teriparatide
16. Diagnosis of autoimmune connective tissue disorder (e.g. lupus erythematosus, scleroderma)
17. Active or recent (less than 12 months) gastroesophageal reflux disease (GERD) unless treated with H2RAs not PPI.
18. 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)
19. 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 12 months post implant procedure
20. 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

21. Active H. pylori
22. History of Crohn's disease, atresias or untreated stenoses
23. Abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or upper gastrointestinal bleeding conditions within 3 months of randomization
24. Any condition or major illness that places the patient at undue risk by participating in the study, including but not limited to, patients at significant risk for surgery because of potential need for surgery to address adverse events
25. Poor dentition not allowing complete chewing of food
26. Enrolled in another investigational study within 3 months of screening for this study (enrollment in observational studies is permitted)
27. Residing in a location without ready access to study site medical resources
28. Documented weight loss of 5% total body weight (TBW) anytime during the 3 months preceding randomization
29. Positive Fecal Immunochemical Test (FIT) at time of screening
30. History or observation of psychological disorder or behavior which could preclude compliance to the treatment and follow up plan
31. No access to an active telephone and internet service for provision of Follow Up Schedule calls and electronic diary
32. 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
33. Any condition that increases red cell turnover, such as thalassemia
34. Existence of (>5 cm string test) Pseudomonas aeruginosa, Stenotrophomonas maltophilia and/or Klebsiella pneumoniae serotype K1 and K2
35. A known sensitivity to nickel or titanium
36. Do not meet the screening criteria for MRI (i.e., MRI unsafe, or MRI conditional but not appropriate for the region of interest)
37. Current use of insulin
38. Patients with history or suspicion of coronary artery disease