Acute Effect of Exenatide on Brain Glucose Metabolism

Study Overview
=================
Brief Summary
-----------------
This research study will examine brain glucose metabolism after an overnight fast to determine the effect of exenatide on brain glucose metabolism and lipid metabolism.

Detailed Description
-----------------
This study will elucidate if exenatide has an effect on brain glucose metabolism. This will be accomplished by measuring the rate of glucose binding in various brain regions by Positron Emission Tomography (PET) after glucose load with exenatide injection and compare it with placebo injection measured in the same subject. The changes will be compared with peripheral and hepatic glucose metabolism and lipolysis.

Official Title
-----------------
Effect of Exenatide on Brain Glucose Uptake in Relations to Pancreatic, Adipose Tissue, and Hepatic Function

Conditions
-----------------
Impaired Glucose Tolerance (IGT), Diabetes

Intervention / Treatment
-----------------
* Drug: Exenatide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males age 18-65 years old Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2 2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes. Patients must have BMI of 25-40 kg/m2 Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study. Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included. Patients must have the following laboratory values: Hematocrit ≥ 34 vol% Serum creatinine* ≤ 1.5 mg/dl in males and Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT): ≤ 2.5 times upper limit of normal Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT): ≤ 2.5 times upper limit of normal Alkaline phosphatase ≤ 2.5 times upper limit of normal If serum creatinine is ≤ 1.5 mg/dl in males, the PI can grant an exception and not exclude the patient if the Glomerular filtration rate (GFR) is >70 ml/min Exclusion Criteria: Patients are excluded from participation in the study if they meet any of the following criteria: Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease) Patients with BMI over 40 and under 25 Patient with age below 18 yrs and over 65 yrs Female subjects Patients with type 1 diabetes Patients treated for type 2 diabetes Subjects with normal glucose tolerance (NGT)

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

Sexes Eligible for Study
-----------------
Male

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide first, then Placebo<br>Exenatide 5mcg was injected subcutaneously 30 min before Oral Glucose Tolerance Test (OGTT)-PET study. The same subject was studied again a few weeks later with the same protocol with Placebo injection. | Drug: Exenatide<br>* Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study<br>* Other names: Byetta;Drug: Placebo<br>* Placebo was administered in random order 30 min before OGTT-PET study in the same subject<br>|
| Experimental: Placebo first, then Exenatide<br>Placebo was injected subcutaneously 30 min before OGTT-PET study. The same subject was studied again a few weeks later with the same protocol with injection of Exenatide 5mcg . | Drug: Exenatide<br>* Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study<br>* Other names: Byetta;Drug: Placebo<br>* Placebo was administered in random order 30 min before OGTT-PET study in the same subject<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism | To study the acute effect of exenatide on brain glucose metabolism after the glucose load. Brain glucose uptake will be determined from serial FDG PET-imaging, by using graphical methods to quantify both global and regional results. The results obtained after Exenatide injection will be compared with the ones obtained after injection of placebo in the same subject. | 120 minutes after exenatide or placebo injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Exenatide on the Liver and Adipose Tissue Glucose Uptake | we evaluated the acute effects of exenatide on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. | 60 minutes after exenatide or placebo injection | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Impaired glucose tolerance (IGT), Diabetes