- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02104739
Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
June 1, 2018 updated by: Absalon D Gutierrez, The University of Texas Health Science Center, Houston
Comparative Effects of Antidiabetic Medications on Postprandial Hyperlipidemia, Free Fatty Acid Signaling, and Endothelial Dysfunction in Individuals With Prediabetes
This project addresses cardiovascular disease risk in patients with prediabetes.
Levels of lipids after eating a meal ("postprandial lipids") are strong independent predictors of cardiovascular risk.
Newer anti-diabetic agents - exenatide and saxagliptin - impact lipid metabolism.
These medications will be studied for their effect in reducing both postprandial lipid levels and arterial dysfunction.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
It is a paradox that medical efforts to control blood glucose in type 2 diabetes mellitus have not decreased the risk of cardiovascular disease.
Postprandial lipid concentrations are a strong predictor of cardiovascular risk, independent of traditional cardiovascular risk factors.
The new classes of antidiabetic medications - GLP-1 agonists and DPP-IV inhibitors - affect lipid as well as glucose metabolism.
This study will investigate the efficacy of these medications in reducing postprandial hyperlipidemia, disrupting the concurrent proinflammatory free fatty acid signaling, and ameliorating endothelial dysfunction in individuals with prediabetes.
This will consist of a single center, randomized, crossover, placebo-controlled double-blinded prospective trial involving three study arms representing the aforementioned medications: exenatide (GLP-1 agonist), saxagliptin (DPP-IV inhibitor), and placebo (control arm).
Each subject will participate in each of the three arms, which are three separate, daylong outpatient studies.
For each study arm, subjects will eat a standardized atherogenic high-fat test lunch.
Venous blood draws and measurements of forearm blood flow will be done prior to the meal and periodically during a 6-hour period after the meal.
Forearm blood flow measurements will assess for changes in endothelial function.
The blood will be analyzed for multiple markers of hyperlipidemia and free fatty acid signaling.
After completing the three randomized study visits, subjects are invited to participate in an optional, nonrandomized extension study.
For the extension study, subjects will take exenatide ER (extended-release exenatide) weekly for total of six weeks.
Then subjects return to eat a standardized atherogenic high-fat test lunch.
Venous blood draws and measurements of forearm blood flow will be done prior to the meal and periodically during a 4-hour period after the meal, for the same analyses described before.
The results will provide new insights into the anti-inflammatory effects of multiple antidiabetic medications via the mechanisms of postprandial hyperlipidemia, free fatty acid signaling, and endothelial function in prediabetic individuals.
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- The University of Texas health Science Center at Houston
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75 gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.7% to 6.4%
- Subjects are allowed, but not required, to be on statins, ACE-inhibitors, beta-blockers, angiotensin-receptor blockers, thiazide diuretics, and/or loop diuretics at doses that have been stable for at least the last 3 months
- BMI between 30-35 kg/m2 (±1 kg/m2)
- Body weight has been stable (±4-5 pounds) over the prior three months.
- Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, or surgical sterilization) for the duration of the study
- Patients must have the following laboratory values: Hematocrit ≥ 34 vol% S. creatinine < 1.5 mg/dl in men and 1.4 mg/dl in women AST (SGOT) < 2.5 times ULN, ALT (SGPT) < 2.5 times ULN, alkaline phosphatase< 2.5 times ULN
Exclusion Criteria:
- History of Type 1 or Type 2 diabetes mellitus
- History of diabetic ketoacidosis or hyperosmolar nonketotic coma
- Pregnant or breastfeeding women
- Patients must not be receiving lipid-lowering medications other than statins within the last 3 months
- Patient must not be receiving metformin, DPP-IV inhibitors, GLP-1 agonists, thiazolidinediones, insulin, sulfonylureas, acarbose, SGLT-2 inhibitors, corticosteroids, or immunosuppressive therapy within the last 3 months and cannot take them for the duration of the study. Patient must not be receiving NSAIDS or antioxidant vitamins within the last 1 week, and cannot take them for the duration of the study.
- Patients must not be on hormone replacement therapy.
- Patients with diabetic gastroparesis
- Patients with current tobacco use
- Patients with active malignancy
- Patients with history of urinary bladder cancer
- Patients with dietary restrictions precluding a high-fat meal
- Patients with a history of clinically significant heart disease (NYHA III or IV; more than non- specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied
- Subjects with a history of any serious hypersensitivity reaction to the study medications
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- Subjects with known allergic reactions to the study medications or test meal
- Subjects unwilling or unable to provide informed consent
- Subjects determined by the investigator(s) to not be appropriate candidates for the study
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Exenatide, then Saxagliptin, then Placebo
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Experimental: Exenatide, then Placebo, then Saxagliptin
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Placebo Comparator: Saxagliptin, then Exenatide, then Placebo
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Experimental: Saxagliptin, then Placebo, then Exenatide
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Experimental: Placebo, then Exenatide, then Saxagliptin
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Experimental: Placebo, then Saxagliptin, then Exenatide
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
|
Experimental: Exenatide, then Saxagliptin, then Placebo, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
Experimental: Exenatide, then Placebo, then Saxagliptin, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
Experimental: Saxagliptin, then Exenatide, then Placebo, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
Experimental: Saxagliptin, then Placebo, then Exenatide, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
Experimental: Placebo, then Exenatide, then Saxagliptin, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
Experimental: Placebo, then Saxagliptin, then Exenatide, then Exenatide ER
Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablet and Placebo (normal saline) injection; Subcutaneous injection (2mg) weekly for 6 weeks
|
Single subcutaneous injection (10 mcg)
Other Names:
Single dose orally (5 mg)
Other Names:
Placebo tablets and Placebo (normal saline) injections
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Monocyte NfkB Levels as Detected by Western Blotting
Time Frame: baseline
|
Monocyte NfkB p65 arbitrary units are quantified by densitometric analysis of the Western blots.
|
baseline
|
Monocyte NfkB Levels as Detected by Western Blotting
Time Frame: 2 hours after ingestion of meal
|
Monocyte NfkB p65 arbitrary units are quantified by densitometric analysis of the Western blots.
|
2 hours after ingestion of meal
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Triglycerides
Time Frame: baseline
|
triglycerides
|
baseline
|
Triglycerides
Time Frame: 2 hours after ingestion of meal
|
triglycerides
|
2 hours after ingestion of meal
|
Triglycerides
Time Frame: 4 hours after ingestion of meal
|
triglycerides
|
4 hours after ingestion of meal
|
Triglycerides
Time Frame: 6 hours after ingestion of meal
|
triglycerides
|
6 hours after ingestion of meal
|
Free Fatty Acids
Time Frame: baseline
|
Free Fatty Acids
|
baseline
|
Free Fatty Acids
Time Frame: 2 hours after meal
|
Free Fatty Acids
|
2 hours after meal
|
Free Fatty Acids
Time Frame: 4 hours after meal
|
Free Fatty Acids
|
4 hours after meal
|
Free Fatty Acids
Time Frame: 6 hours after meal
|
Free Fatty Acids
|
6 hours after meal
|
Peak Forearm Blood Flow
Time Frame: baseline
|
Peak forearm blood flow via strain gauge venous occlusion plethysmography
|
baseline
|
Peak Forearm Blood Flow
Time Frame: 3 hours after meal
|
Peak forearm blood flow via strain gauge venous occlusion plethysmography
|
3 hours after meal
|
Peak Forearm Blood Flow
Time Frame: 6 hours after meal
|
Peak forearm blood flow via strain gauge venous occlusion plethysmography
|
6 hours after meal
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Absalaon D Gutierrez, MD, University of Texas Health Science Center at Houston, Dept. of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2014
Primary Completion (Actual)
March 1, 2017
Study Completion (Actual)
March 1, 2017
Study Registration Dates
First Submitted
April 1, 2014
First Submitted That Met QC Criteria
April 3, 2014
First Posted (Estimate)
April 4, 2014
Study Record Updates
Last Update Posted (Actual)
July 3, 2018
Last Update Submitted That Met QC Criteria
June 1, 2018
Last Verified
June 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Hyperglycemia
- Prediabetic State
- Glucose Intolerance
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Anti-Obesity Agents
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Exenatide
- Saxagliptin
Other Study ID Numbers
- HSC-MS-13-0791
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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