Effects of Antidiabetic Medications on the Postprandial State in Prediabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by The University of Texas Health Science Center, Houston
Sponsor:
Collaborator:
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
Information provided by (Responsible Party):
Absalon D Gutierrez, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT02104739
First received: April 1, 2014
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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, saxagliptin, and pioglitazone - impact lipid metabolism. These medications will be studied for their effect in reducing both postprandial lipid levels and arterial dysfunction.


Condition Intervention Phase
Prediabetes
Obesity
Drug: Exenatide
Drug: Saxagliptin
Drug: Pioglitazone
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Effects of Antidiabetic Medications on Postprandial Hyperlipidemia, Free Fatty Acid Signaling, and Endothelial Dysfunction in Individuals With Prediabetes

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Free Fatty Acids [ Time Frame: 6 hours after ingestion of meal ] [ Designated as safety issue: No ]
    Free Fatty Acids


Secondary Outcome Measures:
  • Triglycerides [ Time Frame: 6 hours after ingestion of meal ] [ Designated as safety issue: No ]
    triglycerides


Other Outcome Measures:
  • Forearm blood flow [ Time Frame: 6 hours after meal ] [ Designated as safety issue: No ]
    Forearm blood flow via strain gauge venous occlusion plethysmography


Estimated Enrollment: 50
Study Start Date: March 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saxagliptin
Saxagliptin 5 mg orally
Drug: Saxagliptin
Single dose orally (5 mg)
Other Name: Onglyza
Experimental: Pioglitazone
Pioglitazone 45 mg orally
Drug: Pioglitazone
Single dose orally (45 mg)
Other Name: Actos
Placebo Comparator: Placebo
Placebo
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Experimental: Exenatide
Exenatide 10 mcg subcutaneously
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Name: Byetta

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, DPP-IV inhibitors, and PPAR-λ agonists - 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 four study arms representing the aforementioned medications: exenatide (GLP-1 agonist), saxagliptin (DPP-IV inhibitor), pioglitazone (PPAR-λ agonist), and placebo (control arm). 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. 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

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women, ages 30 to 70 years of age inclusive
  2. 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%
  3. Subjects are allowed, but not required, to be on statins, ACE-inhibitors, and angiotensin-receptor blockers at doses that have been stable for at least the last 3 months
  4. BMI between 30-35 kg/m2
  5. Body weight has been stable (±4-5 pounds) over the prior three months.
  6. 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
  7. Patients must have the following laboratory values: Hematocrit ≥ 34 vol%, serum creatinine < 1.5 mg/dl in men and <1.4 mg/dl in women, aspartate aminotransferase < 2.5 times upper limit of normal, alanine aminotransferase < 2.5 times upper limit of normal, alkaline phosphatase< 2.5 times upper limit of normal

Exclusion Criteria:

  1. History of Type 1 or Type 2 diabetes mellitus
  2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  3. Pregnant or breastfeeding women
  4. Patients must not be receiving lipid-lowering medications other than statins within the last 3 months
  5. Patient must not be receiving metformin, DPP-IV inhibitors, GLP-1 agonists, thiazolidinediones, insulin, sulfonylureas, acarbose, sodium-glucose cotransporter-2 inhibitors, nonsteroidal antiinflammatory drugs, corticosteroids, immunosuppressive therapy, and antioxidant vitamins within the last 3 months
  6. Patients must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications such as hormone replacement therapy with known adverse effects on glucose tolerance levels.
  7. Patients with diabetic gastroparesis
  8. Patients with current tobacco use
  9. Patients with active malignancy
  10. Patients with history of urinary bladder cancer
  11. Patients with dietary restrictions precluding a high-fat meal
  12. 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
  13. Subjects with a history of any serious hypersensitivity reaction to the study medications
  14. Prisoners, or subjects who are involuntarily incarcerated
  15. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
  16. Subjects with known allergic reactions to the study medications or test meal
  17. Subjects unwilling or unable to provide informed consent
  18. Subjects determined by the investigator(s) to not be appropriate candidates for the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02104739

Contacts
Contact: Absalon D Gutierrez, MD 713-500-6641 absalon.d.gutierrez@uth.tmc.edu
Contact: Monika A Ruscheinsky, MS 713-704-0825 monika.ruscheinsky@uth.tmc.edu

Locations
United States, Texas
University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Absalon D Gutierrez, MD    713-500-6641    absalon.d.gutierrez@uth.tmc.edu   
Contact: Monika A Ruscheinsky, MS    713-704-4137    monika.ruscheinsky@uth.tmc.edu   
Principal Investigator: Absalon D Gutierrez, MD         
Sub-Investigator: Heinrich Taegtmeyer, MD, DPhil         
Sub-Investigator: Philip Orlander, MD         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
Investigators
Principal Investigator: Absalaon D Gutierrez, MD University of Texas Health Science Center at Houston, Dept. of Medicine
  More Information

No publications provided

Responsible Party: Absalon D Gutierrez, Assistant Professor of Medicine, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02104739     History of Changes
Other Study ID Numbers: HSC-MS-13-0791
Study First Received: April 1, 2014
Last Updated: April 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center, Houston:
prediabetes
diabetes mellitus type 2
exenatide
saxagliptin
pioglitazone

Additional relevant MeSH terms:
Obesity
Glucose Intolerance
Prediabetic State
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Pioglitazone
Exenatide
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014