Effect of Prolonged PDE-5 Inhibition on Insulin Signaling in Skeletal Muscle.
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome
Intervention: Sildenafil citrate; Placebo Oral Capsule
Intervention description: Sildenafil citrate 25 mg, 1 capsule three times a day for 3 months; placebo capsules, 1 capsule po three times a day for 3 months
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Our research proposal will determine if PDE-5 inhibition exerts a favorable effect on insulin
      signaling pathways in skeletal muscle of subjects with impaired fasting glucose and/or
      impaired glucose tolerance.
    

Eligibility criteria:

        Inclusion Criteria:

        Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) and ≤40kg/m2 Impaired
        fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (2-hr plasma glucose
        140-199 mg/dL) and/or hemoglobin A1c 5.7-6.4%

        Exclusion Criteria:

          -  Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater, a
             two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic
             medication.

          -  The use of nitrates or any disease that might require the use of nitrates.

          -  The use of any potent CYP3A4 inhibitor.

          -  Subjects who have participated in a weight-reduction program during the last 6 month
             or whose weight has increased or decreased more than 2 kg over the preceding 6 months.

          -  Pregnancy. Women of child-bearing potential will be required to have undergone tubal
             ligation or to be using barrier or hormonal methods of birth control.

          -  Breast-feeding.

          -  Cardiovascular disease such as myocardial infarction within 6 months prior to
             enrollment, presence of angina pectoris, significant arrhythmia, congestive heart
             failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block,
             mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy.

          -  Treatment with anticoagulants.

          -  Treatment with metformin.

          -  History of serious neurologic disease such as cerebral hemorrhage, stroke, or
             transient ischemic attack.

          -  History or presence of immunological or hematological disorders.

          -  Diagnosis of asthma on current inhaled corticosteroid therapy.

          -  Clinically significant gastrointestinal impairment that could interfere with drug
             absorption.

          -  Impaired hepatic function (aspartate amino transaminase and/or alanine amino
             transaminase >1.5 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.