Effects of Antidiabetic Medications on the Postprandial State in Prediabetes

NCT02104739 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HSC-MS-13-0791
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prediabetes; Obesity

Keywords

prediabetes; diabetes mellitus type 2; exenatide; saxagliptin; exenatide ER

Outcome Measures

Primary Outcomes (2)

• Monocyte NfkB Levels as Detected by Western Blotting

  Monocyte NfkB p65 arbitrary units are quantified by densitometric analysis of the Western blots.

  baseline

• Monocyte NfkB Levels as Detected by Western Blotting

  Monocyte NfkB p65 arbitrary units are quantified by densitometric analysis of the Western blots.

  2 hours after ingestion of meal

Secondary Outcomes (11)

• Triglycerides

  baseline

• Triglycerides

  2 hours after ingestion of meal

• Triglycerides

  4 hours after ingestion of meal

• Triglycerides

  6 hours after ingestion of meal

• Free Fatty Acids

  baseline

Study Arms (12)

Exenatide, then Saxagliptin, then Placebo

EXPERIMENTAL

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Exenatide, then Placebo, then Saxagliptin

EXPERIMENTAL

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Saxagliptin, then Exenatide, then Placebo

PLACEBO COMPARATOR

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Saxagliptin, then Placebo, then Exenatide

EXPERIMENTAL

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Placebo, then Exenatide, then Saxagliptin

EXPERIMENTAL

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Placebo, then Saxagliptin, then Exenatide

EXPERIMENTAL

Exenatide Single subcutaneous injection (10 mcg); Saxagliptin Single dose orally (5 mg); Placebo tablets and Placebo (normal saline) injections

Drug: Exenatide; Drug: Saxagliptin; Other: Placebo

Exenatide, then Saxagliptin, then Placebo, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Exenatide, then Placebo, then Saxagliptin, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Saxagliptin, then Exenatide, then Placebo, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Saxagliptin, then Placebo, then Exenatide, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Placebo, then Exenatide, then Saxagliptin, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Placebo, then Saxagliptin, then Exenatide, then Exenatide ER

EXPERIMENTAL

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; Drug: Saxagliptin; Drug: Exenatide extended-release (ER); Other: Placebo

Interventions

Exenatide DRUG

Single subcutaneous injection (10 mcg)

Also known as: Byetta

Exenatide, then Placebo, then Saxagliptin; Exenatide, then Placebo, then Saxagliptin, then Exenatide ER; Exenatide, then Saxagliptin, then Placebo; Exenatide, then Saxagliptin, then Placebo, then Exenatide ER; Placebo, then Exenatide, then Saxagliptin; Placebo, then Exenatide, then Saxagliptin, then Exenatide ER; Placebo, then Saxagliptin, then Exenatide; Placebo, then Saxagliptin, then Exenatide, then Exenatide ER; Saxagliptin, then Exenatide, then Placebo; Saxagliptin, then Exenatide, then Placebo, then Exenatide ER; Saxagliptin, then Placebo, then Exenatide; Saxagliptin, then Placebo, then Exenatide, then Exenatide ER

Saxagliptin DRUG

Single dose orally (5 mg)

Also known as: Onglyza

Exenatide, then Placebo, then Saxagliptin; Exenatide, then Placebo, then Saxagliptin, then Exenatide ER; Exenatide, then Saxagliptin, then Placebo; Exenatide, then Saxagliptin, then Placebo, then Exenatide ER; Placebo, then Exenatide, then Saxagliptin; Placebo, then Exenatide, then Saxagliptin, then Exenatide ER; Placebo, then Saxagliptin, then Exenatide; Placebo, then Saxagliptin, then Exenatide, then Exenatide ER; Saxagliptin, then Exenatide, then Placebo; Saxagliptin, then Exenatide, then Placebo, then Exenatide ER; Saxagliptin, then Placebo, then Exenatide; Saxagliptin, then Placebo, then Exenatide, then Exenatide ER

Exenatide extended-release (ER) DRUG

Subcutaneous injection (2mg) weekly for 6 weeks

Also known as: Bydureon

Exenatide, then Placebo, then Saxagliptin, then Exenatide ER; Exenatide, then Saxagliptin, then Placebo, then Exenatide ER; Placebo, then Exenatide, then Saxagliptin, then Exenatide ER; Placebo, then Saxagliptin, then Exenatide, then Exenatide ER; Saxagliptin, then Exenatide, then Placebo, then Exenatide ER; Saxagliptin, then Placebo, then Exenatide, then Exenatide ER

Placebo OTHER

Placebo tablets and Placebo (normal saline) injections

Exenatide, then Placebo, then Saxagliptin; Exenatide, then Placebo, then Saxagliptin, then Exenatide ER; Exenatide, then Saxagliptin, then Placebo; Exenatide, then Saxagliptin, then Placebo, then Exenatide ER; Placebo, then Exenatide, then Saxagliptin; Placebo, then Exenatide, then Saxagliptin, then Exenatide ER; Placebo, then Saxagliptin, then Exenatide; Placebo, then Saxagliptin, then Exenatide, then Exenatide ER; Saxagliptin, then Exenatide, then Placebo; Saxagliptin, then Exenatide, then Placebo, then Exenatide ER; Saxagliptin, then Placebo, then Exenatide; Saxagliptin, then Placebo, then Exenatide, then Exenatide ER

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hamidi V, Riggs K, Zhu L, Bermudez Saint Andre K, Westby C, Coverdale S, Dursteler A, Wang H, Miller Iii C, Taegtmeyer H, Gutierrez AD. Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial. Metab Syndr Relat Disord. 2020 Jun;18(5):225-233. doi: 10.1089/met.2019.0102. Epub 2020 Mar 31.

  PMID: 32228379 DERIVED

MeSH Terms

Conditions

Prediabetic State; Obesity; Diabetes Mellitus, Type 2

Interventions

Exenatide; saxagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Lower than expected sample size.

Results Point of Contact

• Title: Absalon D Gutierrez, MD
• Organization: The University of Texas Health Science Center at Houston

Absalon.D.Gutierrez@uth.tmc.edu

(713) 500-6641

Study Officials

• Absalaon D Gutierrez, MD

  University of Texas Health Science Center at Houston, Dept. of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo pills and placebo injections provided
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 4, 2014
• Study Start: April 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 3, 2018
• Results First Posted: July 3, 2018

Record last verified: 2018-06

Locations

US (1)