Type 2 Diabetes
Conditions
Brief summary
The purpose of the study was to evaluate the safety and efficacy of the EndoBarrier Gastrointestinal Liner compared to sham control in subjects with Type 2 diabetes.
Detailed description
The study was designed as a randomized, single blind, sham controlled, pilot efficacy study of subjects with Type 2 diabetes enrolled at 2 centers in Santiago, Chile. Subjects were enrolled at a 2:1 ratio (EndoBarrier to sham). Following implantation or sham procedure, subjects were treated for 24 weeks or 52 weeks. Following explant, subjects were followed for an additional 8-12 weeks. Subject evaluations included measurements of HbA1c, glucose, insulin, weight, changes in diabetic medications, and meal tolerance tests. Safety was monitored through the collection of clinical labs, physical assessments, endoscopy and adverse events.
Interventions
The EndoBarrier is a single use, implant consisting of a tube of composite material which is placed in the proximal section of the duodenum. The implant is fixed in place with the aid of a metal anchor. The device is delivered via an endoscope. The implant facilitates the passage of food from the stomach through the tube to the proximal section of the jejunum.
OTHERSham: endoscopy and standard of care
Sham subjects had an endoscopic procedure and then received standard of care treatment of their diabetes
Sponsors
Hospital Dipreca
Morphic Medical Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years and \< 55 years - Male or Female * Patients with type 2 diabetes, treated for 10 years or less * HbA1c level ≥ 7.0 and ≤ 10.0% * Fasting glucose ≤ 240 mg/dl * Patients taking metformin, sulfonylureas or thiazolidinediones (TZDs), either alone or in combination * BMI \> 30 and \<50 * Patients willing to comply with study requirements * Patients who have signed an informed consent form * Women who are post-menopausal, surgically sterile, or on oral contraceptives for at least three months and who do not plan on becoming pregnant during the course of the study.
Exclusion criteria
* Patients taking oral medications to control their diabetes other than sulfonylureas, metformin or thiazolidinediones * Patients diagnosed with type 1 diabetes mellitus or had a history of ketoacidosis * Patients requiring insulin * Patients with lab evidence of probable insulin production failure (fasting C peptide serum level \< 1ng/ml) * Patients with a weight loss of \> 10 lbs within the three months of screening * Patients requiring prescription anticoagulation therapy * Patients with iron deficiency and iron deficiency anemia * Patients with a history of abnormal pathologies of the GI tract * Patients with known gallstones or kidney stones prior to implant * Known infection at the time of implant * Severe coagulopathy, upper gastro-intestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasia * Pregnant or has the intention of becoming pregnant in the next 12 months * Patients with a history of active kidney stones * Mentally retarded or emotionally unstable, or exhibits psychological characteristics which, in the opinion of the investigator, makes the subject a poor candidate for device placement or clinical trial * Previous GI surgery that could affect the ability to place the sleeve or the function of the implant * Patients unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during the implant period * H. pylori positive patients (Note: patients may be enrolled if they had a prior history and were successfully treated) * Patients receiving weight loss medications such as Meridia and Xenical * Family or patient history of a known diagnosis or pre-existing symptom of systemic lupus erythematous, scleroderma or other autoimmune connective tissue disorder * Patients with Gastrointestinal Reflux Disease (GERD) * Participating in another ongoing investigational clinical trial * Patients taking corticosteroids or drugs known to affect gastrointestinal motility (such as reglan)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c Values From Baseline Measurement | Baseline to 24 weeks or 52 weeks | Cohort A: Assessment of improvement in the glycemic control defined as a change in HbA1c values from baseline. Cohort B. Assessment of improvement in glycemic control defined as a change in HbA1c values of at least 0.5% from baseline. |
Secondary
| Measure | Time frame |
|---|---|
| Absolute Weight Change | 24 weeks or 52 weeks |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EndoBarrier Gastrointestinal Liner Subjects randomized and implanted with the EndoBarrier Gastrointestinal liner; subjects will be implanted for 24 weeks to 52 weeks and evaluated for study endpoints.
EndoBarrier Gastrointestinal Liner: The EndoBarrier is a single use, implant consisting of a tube of composite material which is placed in the proximal section of the duodenum. The implant is fixed in place with the aid of a metal anchor. The device is delivered via an endoscope. The implant facilitates the passage of food from the stomach through the tube to the proximal section of the jejunum. | 18 |
| Sham: Endoscopy and Standard of Care Subjects randomized to sham arm received an upper GI examination and were evaluated for study endpoints.
Sham: endoscopy and standard of care: Sham subjects had an endoscopic procedure and then received standard of care treatment of their diabetes | 9 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | non-accommodating anatomy | 0 | 1 | 0 | 0 |
| Overall Study | procedural complication | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | EndoBarrier Gastrointestinal Liner | Sham: Endoscopy and Standard of Care | Total |
|---|---|---|---|
| Age, Continuous Cohort A | 44.8 years STANDARD_DEVIATION 7.96 | 52.1 years STANDARD_DEVIATION 16.14 | 46.9 years STANDARD_DEVIATION 10.75 |
| Age, Continuous Cohort B | 41.2 years STANDARD_DEVIATION 9.28 | 46.3 years STANDARD_DEVIATION 6.25 | 46.1 years STANDARD_DEVIATION 8.36 |
| Gender Female | 13 Participants | 7 Participants | 20 Participants |
| Gender Male | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment Chile | 18 participants | 9 participants | 27 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 25 | 11 / 11 |
| serious Total, serious adverse events | 1 / 25 | 0 / 11 |
Outcome results
Primary
Change in HbA1c Values From Baseline Measurement
Cohort A: Assessment of improvement in the glycemic control defined as a change in HbA1c values from baseline. Cohort B. Assessment of improvement in glycemic control defined as a change in HbA1c values of at least 0.5% from baseline.
Time frame: Baseline to 24 weeks or 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: EndoBarrier Gastrointestinal Liner | Change in HbA1c Values From Baseline Measurement | 2.4 percentage of HbA1c | Standard Deviation 1.96 |
| Cohort B: EndoBarrier Gastrointestinal Liner | Change in HbA1c Values From Baseline Measurement | 2.2 percentage of HbA1c | Standard Deviation 1.44 |
| Cohort A Control Sham: Endoscopy and Standard of Care | Change in HbA1c Values From Baseline Measurement | 0.8 percentage of HbA1c | Standard Deviation 0.81 |
| Cohort B Control Sham: Endoscopy and Standard of Care | Change in HbA1c Values From Baseline Measurement | 1.6 percentage of HbA1c | Standard Deviation 1.05 |
Secondary
Absolute Weight Change
Time frame: 24 weeks or 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: EndoBarrier Gastrointestinal Liner | Absolute Weight Change | 9.9 kg | Standard Deviation 1.7 |
| Cohort B: EndoBarrier Gastrointestinal Liner | Absolute Weight Change | 11.3 kg | Standard Deviation 2 |
| Cohort A Control Sham: Endoscopy and Standard of Care | Absolute Weight Change | 7.9 kg | Standard Deviation 5.4 |
| Cohort B Control Sham: Endoscopy and Standard of Care | Absolute Weight Change | 5.4 kg | Standard Deviation 3.7 |