Acute Effect of Exenatide on Brain Glucose Metabolism

• Sponsor: The University of Texas Health Science Center at San Antonio (Other)
• Overall Status: Completed
• CT.gov ID: NCT01588418
• Collaborator: Amylin Pharmaceuticals, LLC. (Industry)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Impaired Glucose Tolerance (IGT); Diabetes	Drug: Exenatide; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effect of Exenatide on Brain Glucose Uptake in Relations to Pancreatic, Adipose Tissue, and Hepatic Function
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide first, then Placebo 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; Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study; Other Names: Byetta ; Drug: Placebo; Placebo was administered in random order 30 min before OGTT-PET study in the same subject
Experimental: Placebo first, then Exenatide 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; Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study; Other Names: Byetta ; Drug: Placebo; Placebo was administered in random order 30 min before OGTT-PET study in the same subject

Outcome Measures

Primary Outcome Measures

1. Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism [120 minutes after exenatide or placebo injection]

   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.

Secondary Outcome Measures

1. Effect of Exenatide on the Liver and Adipose Tissue Glucose Uptake [60 minutes after exenatide or placebo injection]

   we evaluated the acute effects of exenatide on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texas Diabetes Institute and UTHSCSA	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• The University of Texas Health Science Center at San Antonio
• Amylin Pharmaceuticals, LLC.

Investigators

• Principal Investigator: Amalia Gastaldelli, PhD, UTHSCSA, San Antonio, TX

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ralph DeFronzo, Professor, The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT01588418
• Other Study ID Numbers: 233-GAS-08
• First Posted: May 1, 2012
• Last Update Posted: Nov 24, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ralph DeFronzo, Professor, The University of Texas Health Science Center at San Antonio: Impaired glucose tolerance (IGT); Diabetes
• Additional relevant MeSH terms: Glucose Intolerance; Exenatide

Study Results

Participant Flow

Arm/Group Title	OGTT-PET: Exenatide First Then Placebo	OGTT-PET: Placebo First, Then Exenatide
Arm/Group Description	In the first study subjects received exenatide 5ug injected before OGTT-PET. In the second study (3 to 12 wk after first study), subjects received placebo injection before OGTT-PET	In the first study subjects received placebo injected before OGTT-PET. In the second study (3 to 12 wk after first study), subjects received exenatide injection (5ug) before OGTT-PET
Period Title: Overall Study
STARTED	11	4
COMPLETED	11	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PET With Exenatide vs Placebo Injection
Arm/Group Description	All subjects will receive the same intervention with Exenatide and placebo. Exenatide or placebo will be administered in random order, (i.e. first or second before OGTT-PET study). In the first study IGT male subjects will be randomized to exenatide or placebo injection before OGTT-PET study. In the second study the same subjects will receive placebo or exenatide respectively before OGTT-PET study. The results obtained after Exenatide injection will be compared with the ones obtained after injection of placebo in the same subject.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Region of Enrollment (participants) [Number]
United States	15 100%
BMI (Body Mass Index) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29 (3)
Fasting plasma glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	114 (3)
HbA1c (% of total hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of total hemoglobin]	5.6 (0.1)
2 hour plasma glucose concentration (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	177 (11)

Outcome Measures

1. Primary Outcome

Title	Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism
Description	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.
Time Frame	120 minutes after exenatide or placebo injection

Outcome Measure Data

Analysis Population Description

We studied, in the same subject, the acute effect of injection of exenatide vs placebo on brain glucose metabolism (CMRglu) after the glucose load. We used FDG PET-imaging to quantify global and regional results.

Arm/Group Title	Effect of Exenatide or Placebo on CMRglu
Arm/Group Description	Brain glucose metabolism (CMRglu) during OGTT measured by PET w/ or w/out Exenatide injection
Measure Participants	15
total gray matter CMRglu after Exenatide	0.14 (0.02)
total gray matter CMRglu after Placebo	0.10 (0.01)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Outcome data was not collected

Arm/Group Title	Exenatide First, Then Placebo	Placebo First, Then Exenatide
Arm/Group Description	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. 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	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 . 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
Measure Participants	0	0

Adverse Events

Arm/Group Title	PET With Exenatide or Placebo Injection
Arm/Group Description	This is a crossover study where all subjects received the same intervention with Exenatide and placebo, acutely in random order, (i.e. first or second before OGTT-PET study).
All Cause Mortality
	PET With Exenatide or Placebo Injection
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PET With Exenatide or Placebo Injection
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	PET With Exenatide or Placebo Injection
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

Our study has several potential limitations. It included only men. During OGTT it is difficult to evaluate the separate contributions of glucose and insulin.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.