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

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

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01728116

Acronym

ENDO

Enrollment

325

Registered

2012-11-16

Start date

2012-12-31

Completion date

2016-02-29

Last updated

2017-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Type 2 Diabetes

Keywords

glycemic control, type 2 diabetes, device, obese

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.

Interventions

DEVICEEndoBarrier

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

PROCEDURESham Procedure

Endoscopic evaluation but no device placement

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Primary Efficacy Endpoint: Improvement in HbA1c	Baseline and12 months	Mean Change in HbA1c from Baseline to 12 Months in the mITT population with Bayesian Imputation
Primary Safety Endpoint: Early Device Removal Due to Device-Related SAE	Baseline and 12 Months	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.

Secondary

Measure	Time frame
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
Assessment of Total Cholesterol Change at 12 Months Compared to 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
Systolic BP Change From 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

Countries

United States

Participant flow

Recruitment details

Up to 500 subjects were planned to be randomized into either the EndoBarrier or the sham control arm at a 2:1 ratio, respectively. Due to early termination of the trial, only 325 subjects were randomized with 216 EndoBarrier subjects and 109 sham control subjects.

Pre-assignment details

The mITT population for the primary analyses includes 213 EndoBarrier subjects and 107 sham control subjects. The remaining five (5) subjects (n=3 randomized to device; n=2 randomized to sham) were deemed ineligible before an attempted device placement due to findings identified during the upper endoscopy.

Participants by arm

Arm	Count
EndoBarrier Group Subjects randomized to the device group received the EndoBarrier Gastrointestinal Liner. Subjects also received a prophylactic dose of antibiotics on Procedure Day. Fluoroscopy was also used in conjunction with endoscopy to aid implantation of the EndoBarrier device.	213
Sham Control Group Subjects randomized to the sham control group also underwent an upper endoscopy (without fluoroscopy) according to standard institutional endoscopy practices. Subjects also received a prophylactic dose of antibiotics on Procedure Day.	107
Total	320

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	13	0
Overall Study	Incorrectly enrolled in Study	0	1
Overall Study	Inter-current finding at procedure	1	0
Overall Study	Lost to Follow-up	9	2
Overall Study	Physician Decision	2	0
Overall Study	Procedure/device failure	7	0
Overall Study	Sponsor Terminated Study	106	35
Overall Study	Subject Non-Compliance	2	0
Overall Study	various not noted previously	5	0
Overall Study	Withdrawal by Subject	16	9

Baseline characteristics

Characteristic	EndoBarrier Group	Sham Control Group	Total
Age, Continuous	52.9 years STANDARD_DEVIATION 8.19	51.8 years STANDARD_DEVIATION 8.21	52.5 years STANDARD_DEVIATION 8.2
Baseline BMI	38.4 kg/m2 STANDARD_DEVIATION 5.74	38.3 kg/m2 STANDARD_DEVIATION 5.33	38.4 kg/m2 STANDARD_DEVIATION 5.6
Baseline Weight (lbs)	245.0 lbs STANDARD_DEVIATION 47.46	245.6 lbs STANDARD_DEVIATION 44.2	245.2 lbs STANDARD_DEVIATION 46.32
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants	14 Participants	33 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	194 Participants	93 Participants	287 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Gender Female	127 Participants	69 Participants	196 Participants
Gender Male	86 Participants	38 Participants	124 Participants
HbA1c (%) fasting bloodwork	8.8 percent STANDARD_DEVIATION 0.92	8.9 percent STANDARD_DEVIATION 0.89	8.8 percent STANDARD_DEVIATION 0.91
Race/Ethnicity, Customized American Indian or Alaska Native	6 participants	3 participants	9 participants
Race/Ethnicity, Customized Asian	1 participants	1 participants	2 participants
Race/Ethnicity, Customized Black or African American	44 participants	22 participants	66 participants
Race/Ethnicity, Customized More than one race	1 participants	1 participants	2 participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants	0 participants	0 participants
Race/Ethnicity, Customized Unknown or Not Reported	1 participants	1 participants	2 participants
Race/Ethnicity, Customized White	165 participants	80 participants	245 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	206 / 212	96 / 108
serious Total, serious adverse events	53 / 212	5 / 108

Outcome results

Primary

Primary Efficacy Endpoint: Improvement in HbA1c

Mean Change in HbA1c from Baseline to 12 Months in the mITT population with Bayesian Imputation

Time frame: Baseline and12 months

Population: All randomized subjects who at their baseline endoscopy are judged to be potential recipients of the device (meaning no abnormal pathologies and/or conditions are present). Any subject who has a device enter their body, regardless of eligibility or randomization assignment, is also included in the treatment arm of the mITT population.

Arm	Measure	Value (MEAN)	Dispersion
EndoBarrier Group	Primary Efficacy Endpoint: Improvement in HbA1c	-1.07 Percentage of HbA1c	Standard Deviation 1.5
Sham Control Group	Primary Efficacy Endpoint: Improvement in HbA1c	-0.31 Percentage of HbA1c	Standard Deviation 1.59

Primary

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.