Effect of Saxagliptin Treatment on Myocardial Fat Content, and Monocyte Inflammation

NCT01548651 | Terminated Phase 4 Results

• 1 other identifier: H-29171
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to examine the effect of saxagliptin, an anti-diabetes medication, on hepatic and myocardial fat content and monocyte inflammation in patients with Impaired Glucose Tolerance (IGT).

Conditions

Impaired Glucose Tolerance

Outcome Measures

Primary Outcomes (1)

• Myocardial and Hepatic Fat Content (Percentage)

  The percentage change in hepatic fat (%) and myocardial fat (%) from baseline as measured by magnetic resonance imaging and spectroscopy (MRS).

  6 months

Secondary Outcomes (2)

• Left Ventricular Ejection Fraction (LVEF)(%).

  6 months

• Monocyte Inflammatory Protein NFkappaB(%)

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo 5 mg orally daily for 6 months

Drug: Placebo

Saxagliptin

EXPERIMENTAL

Saxagliptin 5 mg orally daily for 6 months

Drug: Saxagliptin

Interventions

Saxagliptin DRUG

Subjects will be randomized to receive either Saxagliptin 5mg daily orally or placebo for 6 months. All subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma levels of inflammatory markers and C Reactive Protein (CRP), Intracellular Adhesion Molecule (ICAM), vascular cell adhesion molecule (VCAM), plasma lipids, and glucose tolerance (75 gram oral glucose tolerance test) as well as measurement of liver and myocardial fat content and left ventricular systolic and diastolic function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, oral glucose tolerance test, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 months.

Also known as: Onglyza

Saxagliptin

Placebo DRUG

Subjects will be randomized to receive either Saxagliptin 5mg daily orally or placebo for 6 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma levels of inflammatory markers and CRP, ICAM, VCAM, plasma lipids, and glucose tolerance (75 gram oral glucose tolerance test) as well as measurement of liver and myocardial fat content and left ventricular systolic and diastolic function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, oral glucose tolerance test, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 month treatment period.

Placebo

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women with a diagnosis diagnosis of Impaired Glucose Tolerance i.e. fasting plasma glucose less than or equal to 125 mg/dl, 2 hour post 75 gram oral glucose tolerance test (OGTT) plasma glucose between 140-199 mg/dl, glycosylated hemoglobin A1c (HbA1c) less than 6.5% as per American Diabetes Association (ADA) criteria.
• Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.

You may not qualify if:

• Patients must not be on anti-diabetes therapy for treatment of Impaired Glucose Tolerance (IGT) and must have a fasting plasma glucose concentration less or equal to 125 mg/dl.
• Type 1 or Type 2 diabetes mellitus (fasting plasma glucose greater than 125 mg/dl).
• Patients must not be on or have received metformin, thiazolidinediones, sulfonylureas, DPP IV inhibitor, or exenatide/liraglutide treatment for treatment of IGT at any time. 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. Patients taking systemic glucocorticoids will also be excluded.
• Subjects with a history of clinically significant heart disease, peripheral vascular disease, or pulmonary disease.
• Subjects must have a Body Mass Index between 30-35 kg/m2 and stable body weight.
• Subjects must not have clinically significant liver disease (aspartate aminotransferase (AST) \< 2.5 times upper limit of normal, Alanine transaminase (ALT) \< 2.5 times upper limit of normal, Alkaline phosphatase\< 2.5 times upper limit of normal), kidney disease (Serum creatinine \< 1.5 mg/dl in men and 1.4 mg/dl in women) or significant anemia (Hematocrit \< 34 vol%).
• Subjects with a history of any serious hypersensitivity reaction to saxagliptin or a dipeptidyl peptidase 4 (DPP-IV) inhibitor.
• Concomitant treatment with systemic cytochrome P450 3A4 inducers.
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glucose Intolerance

Interventions

saxagliptin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mandeep Bajaj
• Organization: Baylor College of Medicine

bajaj@bcm.edu

713-798-1712

Study Officials

• Mandeep Bajaj, MD

  Baylor College 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: March 8, 2012
• Study Start: February 1, 2012
• Primary Completion: August 25, 2017
• Study Completion: August 25, 2017
• Last Updated: January 13, 2020
• Results First Posted: January 13, 2020

Record last verified: 2019-12

Locations

US (1)