Type I Diabetes
Conditions
Brief summary
The goal of the proposed pilot study is to determine whether glucose control can be improved with Bydureon treatment in patients with type I diabetes (T1D)
Detailed description
This is a multi-site randomized placebo controlled trial of Bydureon in patients with type I diabetes (T1D) of at least 2 years duration who may or may not still have detectable levels of C-peptide during a mixed meal tolerance test (MMTT). Bydureon is a recently approved long acting form of Exenatide. Because of the lack of safety data for Bydureon in children, we propose to conduct the trial in adults (\>18 yrs.). Both the subject and the study personnel will be blinded to treatment assignment. The randomization will be done, 1;1, by the coordinating site (at Yale). As a secondary analysis, we propose to determine whether the presence of residual insulin production modifies the drug effect. To do this, we plan to stratify patients for randomization on the basis of detectable C-peptide levels. We will therefore wait for the results of the C-peptide levels from the enrollment MMTT prior to randomization. The study investigators will not be told in which stratum the patient is being randomized and will be blinded to the C-peptide results of the MMTT until the conclusion of the study. Note: The primary and study completion dates were changed 4/2016 to reflect an extension of the recruitment and accrual periods.
Interventions
DRUGExenatide (Bydureon®)
DRUGPlacebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18-65 years who meets the American Diabetes Association standard T1DM criteria. * Diagnosis of T1DM at least 2 years from Visit 0 * Insulin Requirement of ≤ 0.90 units/kg * Absence of ketoacidosis in the past 6 months * HbA1c of ≥ 6.5% and ≤ 9.5% * Menstruating women must have a negative pregnancy test and be willing to avoid pregnancy during the study period * Signed informed consent
Exclusion criteria
* Inability or unwillingness to give informed consent * Current or prior use of immunomodulators or systemic steroids in the last 6 months that could potentially affect diabetes or immunologic status. * Known hypersensitivity to Exenatide, Liraglutide or any product component. * Participation in an investigational treatment trial within the last 6 weeks before enrollment. * 1 or more episodes of hypoglycemia (loss of consciousness or requiring the help of others) within the last 6 months. * Another condition that would, in the view of the investigator, affect the safety of using Bydureon. This might include, among others a history of MEN 2, a history of medullary carcinoma of the thyroid or pancreatitis. * Known severe renal impairment, end-stage renal disease or renal transplantation. * Any history of gastroparesis or other severe gastrointestinal disease, pancreatitis, thyroid nodules or malignancy with the exclusion of a history of localized basal cell carcinoma. * Uncompensated heart failure, fluid overload, myocardial infarction or liver disease within the last 6 weeks before enrollment. * Clinically active serious infection. * Positive pregnancy test in menstruating women or lactating females. * Concurrent use of Pramlinitide, other Incretin medications, or other anti-diabetes medications other than insulin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in HbA1c Levels | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c Levels | 12 months | — |
| Major Hypoglycemic Event Rate On Drug | Up to 6 months | The hypoglycemic event rate was calculated for patients while on and off study drug. The event rate is calculated using the number of events divided by the number of months either on or off study drug. Major hypoglycemic events are categorized as an event with a blood glucose level \< 55 mg/dL. |
| Major Hypoglycemic Event Rate Off Drug | Up to 12 months | The hypoglycemic event rate was calculated for patients while on and off study drug. The event rate is calculated using the number of events divided by the number of months either on or off study drug. Major hypoglycemic events are categorized as an event with a blood glucose level \< 55 mg/dL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide (Bydureon) 2 mg, of drug administration 1 per week via subcutaneous self injection
Exenatide (Bydureon®) | 40 |
| Placebo 2 mg, 1 per week via subcutaneous placebo self injection
Placebo | 39 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Removed from Study Prior to Receiving Dr | 0 | 1 |
| Overall Study | Stopping Rule: Lost Greater than 5kg | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
| Overall Study | Withdrew Consent Prior to Receiving Drug | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Exenatide (Bydureon) | Total |
|---|---|---|---|
| Age, Continuous | 33.49 years STANDARD_DEVIATION 11.39 | 38.55 years STANDARD_DEVIATION 12.06 | 36.05 years STANDARD_DEVIATION 11.94 |
| BMI (kg/m^2) | 29.41 kg/m^2 STANDARD_DEVIATION 6.34 | 29.31 kg/m^2 STANDARD_DEVIATION 6.35 | 29.36 kg/m^2 STANDARD_DEVIATION 6.31 |
| C-Peptide Production Negative (< 0.05 ng/ml) | 22 Participants | 24 Participants | 46 Participants |
| C-Peptide Production Positive (>= 0.05 ng/ml) | 17 Participants | 16 Participants | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 35 Participants | 34 Participants | 69 Participants |
| Region of Enrollment United States | 39 participants | 40 participants | 79 participants |
| Sex: Female, Male Female | 25 Participants | 29 Participants | 54 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 25 Participants |
| Study Site Joslin Diabetes Center at HMS | 2 Participants | 3 Participants | 5 Participants |
| Study Site SUNY Upstate Medical University | 0 Participants | 4 Participants | 4 Participants |
| Study Site University of California San Francisco | 3 Participants | 5 Participants | 8 Participants |
| Study Site University of Chicago | 3 Participants | 3 Participants | 6 Participants |
| Study Site University of Colorado: Denver | 7 Participants | 6 Participants | 13 Participants |
| Study Site University of Miami | 3 Participants | 0 Participants | 3 Participants |
| Study Site University of Michigan | 4 Participants | 6 Participants | 10 Participants |
| Study Site Yale University | 17 Participants | 13 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 35 |
| other Total, other adverse events | 39 / 39 | 28 / 35 |
| serious Total, serious adverse events | 6 / 39 | 2 / 35 |
Outcome results
Primary
Change From Baseline in HbA1c Levels
Time frame: 6 months
Population: Intention to treat analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide (Bydureon) | Change From Baseline in HbA1c Levels | -0.12 mmol/mol | Standard Error 0.08 |
| Placebo | Change From Baseline in HbA1c Levels | 0.11 mmol/mol | Standard Error 0.1 |
p-value: 0.081695% CI: [-0.5, 0.03]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c Levels
Time frame: 12 months
Population: Intention to treat analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide (Bydureon) | Change From Baseline in HbA1c Levels | 0.08 mmol/mol | Standard Error 0.09 |
| Placebo | Change From Baseline in HbA1c Levels | 0.10 mmol/mol | Standard Error 0.1 |
p-value: 0.91295% CI: [-0.28, 0.25]Mixed Models Analysis
Secondary
Major Hypoglycemic Event Rate Off Drug
The hypoglycemic event rate was calculated for patients while on and off study drug. The event rate is calculated using the number of events divided by the number of months either on or off study drug. Major hypoglycemic events are categorized as an event with a blood glucose level \< 55 mg/dL.
Time frame: Up to 12 months
Population: Only those randomized that received study drug and were followed through study completion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide (Bydureon) | Major Hypoglycemic Event Rate Off Drug | 0.33 events per month |
| Placebo | Major Hypoglycemic Event Rate Off Drug | 0.50 events per month |
p-value: 0.189Wilcoxon (Mann-Whitney)
Secondary
Major Hypoglycemic Event Rate On Drug
The hypoglycemic event rate was calculated for patients while on and off study drug. The event rate is calculated using the number of events divided by the number of months either on or off study drug. Major hypoglycemic events are categorized as an event with a blood glucose level \< 55 mg/dL.
Time frame: Up to 6 months
Population: Only those randomized that received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide (Bydureon) | Major Hypoglycemic Event Rate On Drug | 0.67 events per month |
| Placebo | Major Hypoglycemic Event Rate On Drug | 0.80 events per month |
p-value: 0.423Wilcoxon (Mann-Whitney)