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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon
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
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Names:
  • Byetta
Drug: Saxagliptin
Single dose orally (5 mg)
Other Names:
  • Onglyza
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Drug: Exenatide extended-release (ER)
Subcutaneous injection (2mg) weekly for 6 weeks
Other Names:
  • Bydureon

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Texas Health Science Center, Houston

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 4, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 3, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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