PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction
Condition: Healthy; Obese
MeSH terms: Obesity
Intervention: Tadalafil; Placebo
Intervention description: Tadalafil is an FDA approved, clinically-available drug that inhibits the enzyme phosphodiesterase type 5A (PDE5). Subjects who are randomized to this arm will be provided with 20mg of Tadalafil to take every day for 12 weeks, beginning at their baseline visit.; 100 patients will be randomized to receive a placebo pill. Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
Intervention MeSH terms: Tadalafil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 141.0
Sex: All
Minimum age: 21 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Obesity and its adverse cardiometabolic consequences are major public health problems.
      Several features of obesity contribute to the associated cardiovascular risk and are
      potential targets for intervention. These include insulin resistance and beta cell
      dysfunction, reduced metabolic rate, and impaired aerobic capacity.The purpose of this study
      is to examine if the phosphodiesterase type 5A inhibitor tadalafil improves cardiometabolic
      health in individuals who are obese and insulin resistant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults (ages 21-50)

          -  Obesity (BMI ≥ 30 kg/m2)

          -  Prediabetes on oral glucose tolerance test.

        Exclusion Criteria:

          -  Age <21 or > 50

          -  BMI < 30 kg/m2

          -  Systolic blood pressure (SBP) < 100, > 150 mmHg

          -  Current anti-hypertensive medication use, including diuretics

          -  Current use of organic nitrates

          -  Current use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil)

          -  History of reaction to PDE-5 inhibitors

          -  Known HIV infection

          -  Use of medications that strongly alter CYP3A4 activity

          -  History of myocardial infarction, angina, uncontrolled cardiac arrhythmia, stroke,
             transient ischemic attack, or seizure

          -  Known non-arteritic ischemic optic retinopathy (NAIOR)

          -  History of hearing loss

          -  Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 by the modified diet
             in renal disease (MDRD) equation

          -  Hepatic transaminase (AST and ALT) levels greater than three times the upper limit of
             normal

          -  Known pregnancy or breastfeeding or those unwilling to avoid pregnancy during the
             course of the study

          -  History of priapism

          -  Use in excess of four alcoholic drinks daily

          -  History of diabetes mellitus or use of anti-diabetic medications

          -  Known anemia (men, Hct < 38% and women, Hct <36%)

          -  Menopause

          -  Inability to exercise on a bicycle

          -  Weight > 300 pounds