A Phase II Trial to Examine the Effect of Subcutaneous Exenatide (Bydureon®) on Glucose Control in Patients With Type I Diabetes

Study Overview
=================
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.

Official Title
-----------------
A Phase II Trial to Examine the Effect of Subcutaneous Exenatide (Bydureon®) on Glucose Control in Patients With Type I Diabetes

Conditions
-----------------
Type I Diabetes

Intervention / Treatment
-----------------
* Drug: Exenatide (Bydureon®)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>2 mg, 1 per week via subcutaneous placebo self injection | Drug: Placebo<br> <br> |
| Experimental: Exenatide (Bydureon)<br>2 mg, of drug administration 1 per week via subcutaneous self injection | Drug: Exenatide (Bydureon®)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c Levels |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c Levels |  | 12 months | 
| 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. | Up to 6 months | 
| 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. | Up to 12 months |