Effect of Saxagliptin Treatment on Myocardial Fat Content, and Monocyte Inflammation
Condition: Impaired Glucose Tolerance
MeSH terms: Glucose Intolerance; Inflammation
Intervention: Saxagliptin; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Saxagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 8.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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