Acute Effect of Exenatide on Brain Glucose Metabolism

NCT01588418 | Completed Phase 4 Results

• 1 other identifier: 233-GAS-08
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Impaired Glucose Tolerance (IGT); Diabetes

Keywords

Impaired glucose tolerance (IGT); Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Effect of Exenatide on the Liver and Adipose Tissue Glucose Uptake

  60 minutes after exenatide or placebo injection

Study Arms (2)

Exenatide first, then Placebo

EXPERIMENTAL

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; Drug: Placebo

Placebo first, then Exenatide

EXPERIMENTAL

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; Drug: Placebo

Interventions

Exenatide DRUG

Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study

Also known as: Byetta

Exenatide first, then Placebo; Placebo first, then Exenatide

Placebo DRUG

Placebo was administered in random order 30 min before OGTT-PET study in the same subject

Exenatide first, then Placebo; Placebo first, then Exenatide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males age 18-65 years old
• Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (1)

Texas Diabetes Institute and UTHSCSA

San Antonio, Texas, 78229, United States

Location

Related 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 System. Diabetes. 2015 Oct;64(10):3406-12. doi: 10.2337/db14-1718. Epub 2015 Jun 26.

  PMID: 26116695 RESULT

• 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 Dec;64(6):2028-2037. doi: 10.1002/hep.28827.

  PMID: 27639082 RESULT

MeSH Terms

Conditions

Glucose Intolerance; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Limitations and 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.

Results Point of Contact

• Title: Dr. Ralph DeFronzo
• Organization: University of Texas Health Science Center at San Antonio

defronzo@uthscsa.edu

210-567-6691

Study Officials

• Amalia Gastaldelli, PhD

  UTHSCSA, San Antonio, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 19, 2012
• First Posted: May 1, 2012
• Study Start: July 1, 2010
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: November 24, 2017
• Results First Posted: May 25, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)