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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes type2
• Intervention / Treatment: Device: EndoBarrier Liner; Other: Sham

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 Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephen J Linhares, BS; Phone Number: 774-454-3259; Email: slinhares@gidynamics.com
• Study Contact Backup: Name: Aoife Devery, BS; Phone Number: 617-528-8880; Email: adevery@gidynamics.com

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • MedStar Health Research Institute
      • Contact: Kendra Green; Phone Number: 202-877-5819; Email: kendra.s.green@medstar.net
      • Contact: John Brebbia, MD; Phone Number: 202-877-5819; Email: john.brebbia@medstar.net
      • Principal Investigator: John Brebbia, MD
      • Sub-Investigator: Jean Park, MD
      • Sub-Investigator: Adline Ghazi, MD
      • Sub-Investigator: Nasrin Ansari, MD
  • Florida
    • Miami, Florida, United States, 33166
      • Recruiting
      • University of Miami Hospital
      • Contact: Eli J Monzon; Email: ejm263@med.miami.edu
      • Contact: Nestor De La Cruz, MD; Email: Ndelacruz@med.miami.edu
      • Principal Investigator: Nestor De La Cruz, MD
      • Sub-Investigator: Gianluca Iacobellis, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Michele Ryan, MS; Phone Number: 617-525-8266; Email: 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
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Michigan Medicine, Division of Gastroenterology and Hepatology
      • Contact: Sarah Volk; Phone Number: 734-647-3082; Email: stomanic@med.umich.edu
      • Contact: Adam Neidert, MS; Phone Number: 734-615-0539; Email: 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
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Jefferson University Hospital/Diabetes Research Center
      • Contact: Genine Jensen, RN; Phone Number: 215-955-1978; Email: Genine.Jensen@jefferson.edu
      • Contact: Marsha Simmons, BS, CCRP; Phone Number: 215-955-8405; Email: 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
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Mercado Michael; Phone Number: 713-798-0950; Email: michael.Mercado@bcm.edu
      • Contact: Wasif M Abidi, MD; Phone Number: 713-798-0950; Email: Wasif.Abidi@bcm.edu
      • Principal Investigator: Wasif M Abidi, MD
      • Sub-Investigator: Kalpesh Patel, MD
      • Sub-Investigator: Mandeep Bajaj, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change in HbA1c value from baseline to 12 months.	One year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GI Dynamics
• Collaborators: Biostatistical Consulting, Inc.
• Investigators: Principal Investigator: Christopher C Thompson, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum In: Lancet 1998 Nov 7;352(9139):1558.
• Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.
• 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.
• Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405.
• Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7. doi: 10.2337/dc06-0703.
• Koh-Banerjee P, Wang Y, Hu FB, Spiegelman D, Willett WC, Rimm EB. Changes in body weight and body fat distribution as risk factors for clinical diabetes in US men. Am J Epidemiol. 2004 Jun 15;159(12):1150-9. doi: 10.1093/aje/kwh167.
• Rodbard D. Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. Diabetes Technol Ther. 2009 Jun;11 Suppl 1:S55-67. doi: 10.1089/dia.2008.0132. Erratum In: Diabetes Technol Ther. 2018 Apr;20(4):320.
• Ford ES, Li C, Little RR, Mokdad AH. Trends in A1C concentrations among U.S. adults with diagnosed diabetes from 1999 to 2004. Diabetes Care. 2008 Jan;31(1):102-4. doi: 10.2337/dc07-0565. Epub 2007 Oct 12. No abstract available.
• Detournay B, Cros S, Charbonnel B, Grimaldi A, Liard F, Cogneau J, Fagnani F, Eschwege E. Managing type 2 diabetes in France: the ECODIA survey. Diabetes Metab. 2000 Nov;26(5):363-9.
• Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003 Jan 1;289(1):76-9. doi: 10.1001/jama.289.1.76.
• Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg. 2002 Nov;236(5):554-9. doi: 10.1097/00000658-200211000-00003.
• Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995 Apr 1;122(7):481-6. doi: 10.7326/0003-4819-122-7-199504010-00001.
• Ritz E. Limitations and future treatment options in type 2 diabetes with renal impairment. Diabetes Care. 2011 May;34 Suppl 2(Suppl 2):S330-4. doi: 10.2337/dc11-s242. No abstract available.
• Bennett MC, Badillo R, Sullivan S. Endoscopic Management. Gastroenterol Clin North Am. 2016 Dec;45(4):673-688. doi: 10.1016/j.gtc.2016.07.005. Erratum In: Gastroenterol Clin North Am. 2017 Jun;46(2):xvii.
• Brethauer SA, Chang J, Galvao Neto M, Greve JW. Gastrointestinal devices for the treatment of type 2 diabetes. Surg Obes Relat Dis. 2016 Jul;12(6):1256-61. doi: 10.1016/j.soard.2016.02.031. Epub 2016 Mar 2.
• Frattini F, Borroni G, Lavazza M, Liu X, Kim HY, Liu R, Anuwong A, Rausei S, Dionigi G. New endoscopic procedures for diabetes mellitus type 2 and obesity treatment. Gland Surg. 2016 Oct;5(5):458-464. doi: 10.21037/gs.2016.10.03.
• Laubner K, Riedel N, Fink K, Holl RW, Welp R, Kempe HP, Lautenbach A, Schlensak M, Stengel R, Eberl T, Dederichs F, Schwacha H, Seufert J, Aberle J. Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus: A case control study. Diabetes Obes Metab. 2018 Aug;20(8):1868-1877. doi: 10.1111/dom.13300. Epub 2018 Apr 23.

Helpful Links

• Statistics on ASMBS 2016
• VeroScience L. Prescribing Information - Cycloset (bromocriptine mesylate) tablets. 2010
• GmbH BII. Prescribing Information - Tradjenta (linagliptin) tablets 2011
• Merck & Co. I. Prescribing information: Januvia (sitagliptin) tablets. 2011:1-23.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Diabetes Mellitus, Type 2; Obesity
• Other Study ID Numbers: 18-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes