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

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

To determine if the EndoBarrier safely and effectively improves glycemic control in obese subjects with type 2 diabetes

Study Overview

• Status: Terminated
• Conditions: Obesity; Type 2 Diabetes
• Intervention / Treatment: Device: EndoBarrier; Procedure: Sham Procedure

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.

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Diagnostic Center (LRDC)
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado/ Anschutz Health & Wellness Center
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Kentucky
    • Louisville, Kentucky, United States, 40218
      • Kentucky Research Group
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2699
      • Tulane University Health Sciences Center
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • Medstar Health Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Minnesota
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97232
      • Legacy Research Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Endocrinology Consultants of East Tennessee & Gastrointestinal Associates
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes
    • Dallas, Texas, United States, 75390-7170
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The Methodist Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Device (EndoBarrier); Device for glycemic control	Device: EndoBarrier; 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; Other Names: Duodenal-jejunal bypass liner (DJBL)
Sham Comparator: Sham Procedure; sham procedure	Procedure: Sham Procedure; Endoscopic evaluation but no device placement

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	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

Collaborators and Investigators

• Sponsor: GI Dynamics
• Investigators: Study Chair: Lee M Kaplan, MD, PhD, Massachusetts General Hospital; Study Director: Keith Gersin, MD, Carolinas Medical Center

Publications and helpful links

Helpful Links

• GI Dynamics website

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: November 13, 2012
• First Posted (Estimate): November 16, 2012

Study Record Updates

• Last Update Posted (Estimate): February 1, 2017
• Last Update Submitted That Met QC Criteria: December 2, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: glycemic control, type 2 diabetes, device, obese
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 09-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes