New Onset Type 1 Diabetes: Role of Exenatide

Study Overview
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Brief Summary
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There are many recent advances in insulin treatment of type 1 diabetes, however after a meal sugars are always a concern. There is a drug Exenatide (Byetta) which is FDA approved to treat people with type 2 diabetes which helps correct their glucoses (sugars) after meals. This study is going to test whether this drug can improve the after meal sugars in people with new onset type 1 diabetes. To test this you will be given a dose of exenatide (1.25 mcg) and long acting insulin or inulin alone before the boost. There is also a placebo group (healthy subjects) who do not get any medication before the boost. Insulin levels and other hormones that affect blood glucose as well as your sugar will be measured by a series of blood tests. The role exenatide as compared to insulin alone will be examined to prevent low blood sugars which might occur because of food staying longer in the stomach than usual or due to the suppression of a hormone called glucagon which increases blood sugar. If you qualify you will be given exenatide (Byetta 1.25 mcg) along with insulin or insulin alone. You and the researchers will not know which dose you are taking at any single visit. A total of 20 people in which some will be children aged 12- 18 years will participate, being diagnosed within 3 months of having been found to have type 1 diabetes.

Detailed Description
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The specific aims of this study are to determine the following: The role of exenatide as compared to insulin monotherapy in reducing postprandial hyperglycemia. The role of exenatide on postprandial glucagon and gastric emptying. The effect of long acting insulin on postprandial glucose excursions, glucagon concentrations and gastric emptying. Postprandial glucose excursions, glucagon concentrations and gastric emptying in normal healthy controls. Study Design: A randomized, non-blinded trial with a crossover design will be used. Following informed consent and with appropriate subject assent, all subjects will have a screening visit. Following the screening visit, subjects with T1DM will undergo 3 studies: Part A (exenatide and long acting insulin), Part B (rapid and long acting insulin) and Part C (long acting insulin only). The subjects will be admitted to the CRC on three separate occasions, at least 3-4 weeks apart. The three studies will be performed in a random order and the randomization will be done using a computerized system. The healthy controls will undergo a single study visit. Except for the absence of diabetes, the healthy controls will be identical to the study subjects. Subjects with new onset diabetes will be compared to healthy controls. During the study, if blood glucose values in a subject are less than 55 mg/dl, IV glucose of 5-15 grams will be administered to achieve euglycemia (90-130 mg/dl). 1-2 doses of IV glucose should correct hypoglycemia. If more than 3 doses are required to achieve euglycemia, the study will be terminated, the subject will be offered a meal tray and blood sugar rechecked to ensure euglycemia. If blood sugar at any time is more than 350 with moderate ketones, the study will be terminated. At around 1 PM (270 min), lunch will be provided (consistent carbohydrate meal) and insulin will be given as per the subject's prescribed regimen. The subject will be discharged home with a designated driver due to the risk of hypoglycemia. A subject will be withdrawn from participating in the study if he/she meets any of the following conditions: 1)develops a chronic disease 2)develops anemia 3)becomes pregnant 4)develops a weight loss of greater than 10 pounds for unspecified reasons 5)loss of contact- if the investigators are unable to reach a study subject (within 2 months of screening or completion of the first study) by phone or mail to schedule the next appointment. All study subjects (that are withdrawn from the study) will receive a phone call and a letter notifying them that they have been withdrawn.

Official Title
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New Onset Type 1 Diabetes: Role of Exenatide

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Exenatide
* Drug: Rapid and long acting insulin
* Drug: long acting insulin + rapid acting + 1.25 mcg Exenatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 12-18 years of age at the time of enrollment. Diagnosed with antibody positive T1DM in the past 3 months. Otherwise healthy except for their TIDM and treated hypothyroidism. Females must have a negative pregnancy test. Hemoglobin equal to or greater than 12 g/dl before each study. Weight greater than 44 kg. Exclusion Criteria: Any chronic disease: leukemia, inflammatory bowel disease, cystic fibrosis, juvenile rheumatoid arthritis etc, except for diabetes and hypothyroidism. Any medications that may affect glucose metabolism. Abnormal AST, ALT, amylase, lipase, creatinine (more than 3 times normal values). Lack of a supportive family environment as detected by the clinicians and/or social workers. History of substance abuse (evaluated by medical history and CRAFFT questionnaire which will be administered at the screening visit). Positive pregnancy test in females. Lactating and nursing mothers.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Exenatide and long acting insulin before the boost. | Drug: Exenatide<br>* 1.25 mcg before the boost sub-cutaneously.<br>* Other names: Byetta;|
| Active Comparator: Part B<br>Rapid and long acting insulin before the boost | Drug: Rapid and long acting insulin<br>* Depends on their Carbohydrate ratio and body needs<br>* Other names: Lantus/ Levemir;|
| Active Comparator: Part C<br>long acting insulin+ rapid acting+1.25 mcg Exenatide before the boost | Drug: long acting insulin + rapid acting + 1.25 mcg Exenatide<br>* Depends on their body needs.<br>* Other names: Levemir;|
| No Intervention: Healthy controls<br>healthy controls without any medication before the boost. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Role of Exenatide as Compared to Insulin Monotherapy in Reducing Postprandial Hyperglycemia. | Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted. | February 2013 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Role of Exenatide on Postprandial Glucagon and Gastric Emptying. | Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted. | February 2013 | 
| Postprandial Glucose Excursions, Glucagon Concentrations and Gastric Emptying in Normal Healthy Controls. | Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted. | February 2013 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes Milletus, diabetes, healthy controls, exenatide, byetta