Safety and Efficacy of EndoBarrier in Subjects With Type 2 Diabetes Who Are Obese

Study Overview
=================
Brief Summary
-----------------
To determine if the EndoBarrier safely and effectively improves glycemic control in obese subjects with type 2 diabetes

Detailed Description
-----------------
This is a randomized, double blinded, prospective study. Subjects will be evaluated and randomized to either the device or sham treatment group if they qualify for the study. A comparison of glycemic control between the two groups will be assessed as the primary outcome measurement as well as the safety profile of the device.

Official Title
-----------------
A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Comparing the EndoBarrier Gastrointestinal Liner System vs. Sham for Glycemic Improvement in Inadequately Controlled Obese Type 2 Diabetic Subjects on Oral Anti-Diabetes Agents

Conditions
-----------------
Type 2 Diabetes, Obesity

Intervention / Treatment
-----------------
* Device: EndoBarrier
* Procedure: Sham Procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males/females aged ≥ 21 years and ≤ 65 years Diagnosis of Type 2 Diabetes for ≤ 20 years Obese individuals (BMI ≥ 30 kg/m2 and ≤ 55 kg/m2) Stable doses (at least 3 months) of up to two anti-T2DM medications (MET, SU, DPP-4i or TZD) Glycemic state: HbA1c at screening ≥ 7.5% and ≤ 10.0%. Subjects willing to comply with study requirements Subjects who have signed an informed consent form Exclusion Criteria: Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis C-peptide < 1.0 ng/mL Triglyceride level > 400 mg/dL Vitamin D deficiency (<20 ng/mL) Male subjects with serum Creatinine >1.5 mg/dl or female subjects with Creatinine >1.4 mg/dL Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy Height < 5 feet (152.4 cm) Current alcohol or drug addiction Symptomatic kidney stones or gallstones within 6 months prior to randomization Chronic pancreatitis or acute pancreatitis within 12 months of randomization Diagnosis of osteoporosis or currently taking bisphosphonates or teriparatide Diagnosis of an autoimmune connective tissue disorder (e.g., lupus erythematosus, scleroderma) Active gastroesophageal reflux disease [GERD] uncontrolled with a Proton Pump Inhibitor (PPI) Thyroid disease unless controlled with medication Currently taking Non-Steroidal Anti-Inflammatory Drugs [NSAIDs] (e.g., aspirin, ibuprofen, etc.) within 10 days prior to randomization and/or there is a need or expected use of these agents during the trial 12 months post index procedure 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 index procedure Currently taking systemic corticosteroids, drugs known to affect GI motility, prescription/over-the-counter weight loss medications, or medications known to cause significant weight gain or weight loss 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 Medication for type 2 diabetes other than MET, SU, DPP-4i, and TZD (e.g., GLP1 or insulin) within 3 months of screening Chronic use of narcotics, opiates, benzodiazepines, or other addictive tranquilizers Allergy or hypersensitivity to ceftriaxone, cephalosporins, penicillin, or any equivalent antibiotics Active Helicobacter pylori infection (Note: Subjects may be eligible after undergoing 2 weeks of antibiotic treatment without re-screening) Previous GI surgery or abnormal GI anatomical finding that could preclude the ability to place the EndoBarrier device, liner or affect the function of the liner Abnormal pathologies or conditions of the gastrointestinal tract, including current ulcers or Crohn's disease, history of atresias or untreated stenoses, current upper gastrointestinal bleeding conditions within 3 months of randomization Any condition or major illness that places the subject at undue risk by participating in the study Poor dentition not allowing complete chewing of food Enrolled in another investigational study within 3 months of screening for this study (Enrollment in observational studies is permitted) Residing in a location without ready access to study site medical resources Documented weight loss of >10 pounds anytime during the 3 months preceding randomization Positive stool guaiac at time of screening

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device (EndoBarrier)<br>Device for glycemic control | Device: EndoBarrier<br>* Endoscopically-delivered and removable device comprised of an anchor that is placed in the duodenal bulb and a 60 cm long impermeable liner that passes distal from the anchor point<br>* Other names: Duodenal-jejunal bypass liner (DJBL);|
| Sham Comparator: Sham Procedure<br>sham procedure | Procedure: Sham Procedure<br>* Endoscopic evaluation but no device placement<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint: Improvement in HbA1c | Mean Change in HbA1c from Baseline to 12 Months in the mITT population with Bayesian Imputation | Baseline and12 months | 
| Primary Safety Endpoint: Early Device Removal Due to Device-Related SAE | Of the 161 subjects for whom data were available at 12 Months, 19 (11.8%) subjects experienced device-related SAEs that required an early device removal. | Baseline and 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Total Cholesterol Change at 12 Months Compared to Baseline |  | Baseline and 12 Months | 
| Percentage of Subjects Who Achieve HbA1c Less Than or Equal to 7.0% at 12 Months |  | Baseline and 12 Months | 
| LDL Change From Baseline |  | Baseline and 12 Months | 
| Triglycerides Change From Baseline |  | Baseline and 12 Months | 
| Fasting Glucose Change From Baseline |  | Baseline and 12 Months | 
| Systolic BP Change From Baseline |  | Baseline and 12 Months | 
| Diastolic BP Change From Baseline |  | Baseline and 12 Months | 
| Percentage of Subjects Who Achieve % Total Body Weight Loss Greater Than or Equal to 5% at 12 Months |  | Baseline and 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
glycemic control, type 2 diabetes, device, obese