Acute Effect of Exenatide on Brain Glucose Metabolism

Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01588418
• Other study ID #: 233-GAS-08
• Status: Completed
• Phase: Phase 4
• First received: March 19, 2012
• Last updated: October 19, 2017
• Start date: July 2010
• Est. completion date: July 2015

Study information

• Verified date: October 2017
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males age 18-65 years old

2. Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2

3. 2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes.

4. Patients must have BMI of 25-40 kg/m2

5. Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study.

6. Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.

7. 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:

1. Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease)

2. Patients with BMI over 40 and under 25

3. Patient with age below 18 yrs and over 65 yrs

4. Female subjects

5. Patients with type 1 diabetes

6. Patients treated for type 2 diabetes

7. Subjects with normal glucose tolerance (NGT)

Related Conditions & MeSH terms

• Diabetes
• Glucose Intolerance
• Impaired Glucose Tolerance (IGT)

Intervention

Drug:
• Exenatide
Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study
• Placebo
Placebo was administered in random order 30 min before OGTT-PET study in the same subject

Locations

Country	Name	City	State
United States	Texas Diabetes Institute and UTHSCSA	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Amylin Pharmaceuticals, LLC.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Daniele G, Iozzo P, Molina-Carrion M, Lancaster J, Ciociaro D, Cersosimo E, Tripathy D, Triplitt C, Fox P, Musi N, DeFronzo R, Gastaldelli A. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward Sys — View Citation

Gastaldelli A, Gaggini M, Daniele G, Ciociaro D, Cersosimo E, Tripathy D, Triplitt C, Fox P, Musi N, DeFronzo R, Iozzo P. Exenatide improves both hepatic and adipose tissue insulin resistance: A dynamic positron emission tomography study. Hepatology. 2016 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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