Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome
Condition: Metabolic Syndrome; Hypertension
MeSH terms: Hypertension; Metabolic Syndrome; Syndrome
Intervention: Placebo; Enalapril 5mg; Enalapril 10mg; Sitagliptin
Intervention description: Enalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d; Enalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d; Enalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d; Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
Intervention MeSH terms: Sitagliptin Phosphate; Enalapril; Enalaprilat
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Metabolic syndrome; Hypertension; Sitagliptin; Enalapril

Summary:

      This study will measure the effect of the anti-diabetic agent sitagliptin on blood pressure
      in individuals with the metabolic syndrome. We will also measure the effect of sitagliptin on
      blood pressure in people already taking a blood pressure medication called an ACE inhibitor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ambulatory subjects, 18 to 70 years of age, inclusive

          -  For female subjects, the following criteria must be met:

               -  Postmenopausal for at least 1 year, or

               -  Status-post surgical sterilization, or

               -  If of childbearing potential, utilization of barrier contraceptive and
                  willingness to undergo beta-hcg testing prior to drug treatment and on every
                  study day

          -  Metabolic syndrome as defined by 3 or more of the following:

               -  Fasting plasma glucose of at least 100 mg/dL (5.6 mmol/L)

               -  Serum triglycerides of at least 150 mg/dL (1.7 mmol/L)

               -  Serum HDL less than or equal to 40 mg/dL in men or less than 50 mg/dL in women or
                  on cholesterol-lowering medications

               -  Blood pressure of at least 130/85 mmHg or on blood-pressure lowering medications

               -  Waist girth of more than 102 cm in med or 88 cm in women

          -  Statin therapy for hypercholesterolemia must be a steady dose for 6 months prior to
             study day

        Exclusion Criteria:

          -  Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater or
             the use of anti-diabetic medication

          -  History of reported or recorded hypoglycemia (plasma glucose less than 70 mg/dL)

          -  Use of hormone replacement therapy

          -  In hypertensive patients, a seated systolic blood pressure greater than 179 mmHg or a
             seated diastolic blood pressure greater than 110 mmHg

          -  Pregnancy

          -  Breast-feeding

          -  Cardiovascular disease such as myocardial infarction within 6 months prior to
             enrollment, presence of angina pectoris, significant arrhythmia, congestive heart
             failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second
             or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic
             cardiomyopathy

          -  Treatment with anticoagulants

          -  History of serious neurological disease such as cerebral hemorrhage, stroke, or
             transient ischemic attack

          -  History or presence of immunological or hematological disorders

          -  Diagnosis of current asthma

          -  History of angioedema associated with use of ACE-I

          -  Clinically significant gastrointestinal impairment that could interfere with drug
             absorption

          -  Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino
             transferase [ALT] > 2.0 x upper limit of normal range)

          -  Impaired renal function (serum creatinine > 1.5 mg/dl)

          -  Hematocrit <35%

          -  Any underlying or acute disease requiring regular medication which could possibly pose
             a threat to the subject or make implementation of the protocol or interpretation of
             the study results difficult

          -  Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days
             in 1 month)

          -  Treatment with lithium salts

          -  History of alcohol or drug abuse

          -  Treatment with any investigational drug in the 1 month preceding the study

          -  Mental conditions rendering the subject unable to understand the nature, scope and
             possible consequences of the study

          -  Inability to comply with the protocol, e.g. uncooperative attitude, inability to
             return for follow-up visits, and unlikelihood of completing the study

          -  Oral contraceptives