EndoBarrier System Pivotal Trial(Rev E v2) (STEP-1)

• ClinicalTrials.gov Identifier: NCT04101669
• Recruitment Status: Recruiting
• First Posted: September 24, 2019
• Last Update Posted: May 11, 2023
• Sponsor: GI Dynamics
• Collaborator: Biostatistical Consulting, Inc.
• Information provided by (Responsible Party): GI Dynamics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Diabetes type2; Obesity	Device: EndoBarrier Liner; Other: Sham	Not Applicable

Detailed 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A multi-center, double-blinded, randomized, sham-controlled trial to evaluate the safety and effectiveness of the EndoBarrier System. Patients will be randomized 3 (EndoBarrier):1 (Sham).
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: The Investigators include interventional gastroenterologists (GI) and endocrinologists. The GI team: MD, PA and site coordinator, as well as radiology personnel will not be masked, while the endocrinologist team: the MDs, PAs, site coordinators and nutritionists, will be masked. The patient is also masked.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 9, 2019
• Estimated Primary Completion Date: April 1, 2024
• Estimated Study Completion Date: April 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: EndoBarrier; Patients in ARM 1, will receive an upper endoscopy and will be treated with the EndoBarrier Liner	Device: EndoBarrier Liner; The EndoBarrier System is provided as a single-use, sterile device and consists of an EndoBarrier Liner preloaded, packaged and sterilized within the EndoBarrier Delivery System. The EndoBarrier Delivery System is utilized to deliver the EndoBarrier Liner to the proximal small intestine. The EndoBarrier Liner is removed using the EndoBarrier Retrieval System. The EndoBarrier System incorporates no pharmacological, biological tissue or blood products.; Other Names: EndoBarrier Sleeve; Duodenal-jejunal Bypass Liner (DJBL)
Sham Comparator: Sham; Patients in Arm 2 will receive an upper endoscopy, but will not be treated with the EndoBarrier Liner.	Other: Sham; Patient receives upper endoscopy but no treatment

Outcome Measures

Primary Outcome Measures :

1. Change in HbA1c [ Time Frame: One year ]
   Change in HbA1c value from baseline to 12 months.

Secondary Outcome Measures :

1. HbA1c value [ Time Frame: 1 and 2 years ]
   Proportion of patients who achieve an HbA1c value of < 7 % by 12 months (52 weeks).
2. Weight Loss [ Time Frame: 1 and 2 years ]
   Proportion of patients who achieve percent total body weight loss ≥ 5% from baseline
3. Insulin use [ Time Frame: 1 and 2 years ]
   Proportion of patients initiating insulin
4. LDL cholesterol [ Time Frame: 1 and 2 years ]
   Change in LDL cholesterol
5. Triglycerides [ Time Frame: 1 and 2 years ]
   Change in triglycerides
6. Lower risk of CKD progression [ Time Frame: 1 and 2 years ]
   Assessment of eGFR
7. Lower risk of development of CKD [ Time Frame: 1 and 2 years ]
   Assessment of eGFR
8. Change in risk for kidney disease [ Time Frame: 1 and 2 years ]
   Combined changes in eGFR and Albuminuria
9. Blood pressure [ Time Frame: 1 and 2 years ]
   Change in systolic blood pressure values
10. Change in daily fasting glucose level [ Time Frame: 1 and 2 years ]
    Change in fasting blood glucose values as measured by daily glucometer reading in mg/dL
11. Change in Nonalcoholic Fatty Liver Disease (NAFLD) [ Time Frame: 1 and 2 years ]
    Change in NAFLD, change in % liver fat using MRI (proton density fat fraction)
12. Change in Nonalcoholic Steatohepatitis (NASH) [ Time Frame: 1 and 2 years ]
    NASH- liver fibrosis % compared to baseline using using MRE measured in kPa
13. Questionnaire [ Time Frame: 1 and 2 years ]
    Change from baseline in treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire (DTSQ)
14. Questionnaire [ Time Frame: 1 and 2 years ]
    Impact of weight on quality of life (IWQOL)

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Stephen J Linhares, BS; 774-454-3259; slinhares@gidynamics.com

Contact: Aoife Devery, BS; 617-528-8880; adevery@gidynamics.com

Locations

United States, District of Columbia

MedStar Health Research Institute; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Kendra Green 202-877-5819 kendra.s.green@medstar.net

Contact: John Brebbia, MD 202-877-5819 john.brebbia@medstar.net

Principal Investigator: John Brebbia, MD

Sub-Investigator: Jean Park, MD

Sub-Investigator: Adline Ghazi, MD

Sub-Investigator: Nasrin Ansari, MD

United States, Florida

University of Miami Hospital; Recruiting

Miami, Florida, United States, 33166

Contact: Eli J Monzon ejm263@med.miami.edu

Contact: Nestor De La Cruz, MD Ndelacruz@med.miami.edu

Principal Investigator: Nestor De La Cruz, MD

Sub-Investigator: Gianluca Iacobellis, MD

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Michele Ryan, MS 617-525-8266 mryan@bwh.harvard.edu

Principal Investigator: Christopher C Thompson, MD

Sub-Investigator: Pichamol Jirapinyo, MD

Sub-Investigator: Marvin Ryou, MD

Sub-Investigator: Meghan Ariagno, MD

Sub-Investigator: Caroline Apovian, MD

United States, Michigan

Michigan Medicine, Division of Gastroenterology and Hepatology; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Sarah Volk 734-647-3082 stomanic@med.umich.edu

Contact: Adam Neidert, MS 734-615-0539 aneidert@med.umich.edu

Principal Investigator: Allison R Schulman, MD

Sub-Investigator: Elif A Oral, MD

Sub-Investigator: Richard s Kwon, MD

Sub-Investigator: Andrew T Krafton, MD

United States, Pennsylvania

Jefferson University Hospital/Diabetes Research Center; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contact: Genine Jensen, RN 215-955-1978 Genine.Jensen@jefferson.edu

Contact: Marsha Simmons, BS, CCRP 215-955-8405 Marsha.Simmons@jefferson.edu

Principal Investigator: Austin L Chiang, MD

Sub-Investigator: Eric J Schiffrin, MD

Sub-Investigator: Thomas E Kowalski, MD

Sub-Investigator: Alexander Schlachterman, MD

Sub-Investigator: David E Loren, MD

Sub-Investigator: Serge A Jabbour, MD

United States, Texas

Baylor College of Medicine; Recruiting

Houston, Texas, United States, 77030

Contact: Mercado Michael 713-798-0950 michael.Mercado@bcm.edu

Contact: Wasif M Abidi, MD 713-798-0950 Wasif.Abidi@bcm.edu

Principal Investigator: Wasif M Abidi, MD

Sub-Investigator: Kalpesh Patel, MD

Sub-Investigator: Mandeep Bajaj, MD

Sponsors and Collaborators

GI Dynamics

Biostatistical Consulting, Inc.

Investigators

• Principal Investigator: Christopher C Thompson, MD; Brigham and Women's Hospital

More Information

Additional Information:

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Torquati A, Lutfi R, Abumrad N, Richards WO. Is Roux-en-Y gastric bypass surgery the most effective treatment for type 2 diabetes mellitus in morbidly obese patients? J Gastrointest Surg. 2005 Nov;9(8):1112-6; discussion 1117-8. doi: 10.1016/j.gassur.2005.07.016.

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• Responsible Party: GI Dynamics
• ClinicalTrials.gov Identifier: NCT04101669
• Other Study ID Numbers: 18-1
• First Posted: September 24, 2019
• Last Update Posted: May 11, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by GI Dynamics:

Type 2 Diabetes; Obesity

Additional relevant MeSH terms:

Obesity; Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight