Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
Condition: Impaired Glucose Tolerance
MeSH terms: Glucose Intolerance
Intervention: Sildenafil; Placebo; Hyperglycemic clamp; Euglycemic clamp
Intervention description: Sildenafil 25 mg by mouth three times a day for three months; Matching placebo three times a day for three months; Subjects with prediabetes will have a baseline hyperglycemic clamp (Aim 1) and then receive sildenafil or placebo for 3 months. Another hyperglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test.; Subjects with prediabetes will have a baseline euglycemic clamp (Aim 2) and then receive sildenafil or placebo for 3 months. Another euglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test.
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BMI greater than 25; Elevated fasting blood sugar (100-125mg/dL)

Summary:

      The purpose of this study is to determine the effect of chronic PDE5 inhibitor therapy on
      glucose metabolism in persons with prediabetes.
    

Eligibility criteria:

        Inclusion criteria:

        Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) Elevated fasting
        plasma glucose (100-125 mg/dL) IGT (2 hour plasma glucose 140-199 mg/dL) OR metabolic
        syndrome 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 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 (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.

          -  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.

          -  Clinically significant gastrointestinal impairment that could interfere with drug
             absorption.

          -  Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino.

        transaminase [ALT] >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 the study