Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?
Condition: Arthritis, Rheumatoid; Atherosclerosis
MeSH terms: Arthritis; Arthritis, Rheumatoid; Atherosclerosis
Intervention: Sildenafil; Placebo
Intervention description: Sildenafil 50 mg once daily; Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Arthritis, Rheumatoid; Atherosclerosis

Summary:

      The purpose of this study is to determine whether sildenafil improves parameters of vascular
      function and blood markers involved in development of heart disease in patients with
      rheumatoid arthritis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meets 2010 American College of Rheumatology (ACR) classification criteria for
             diagnosis of RA

          -  Aged 18 years or older

          -  No known history of CVD (see Exclusion Criteria)

          -  At least one traditional CV risk factor (i.e., older age [men ≥45 years, women ≥55
             years], obesity [defined as body mass index (BMI) >30 kg/m2], smoking, hypertension,
             hyperlipidemia, diabetes mellitus, family history of premature [defined as diagnosed
             at <65 years old] CVD in first-degree relative)

          -  On stable baseline doses of RA medications, defined as no change in dose within past 4
             weeks and no anticipated changes over the next 6 months

          -  On no higher than 10 mg per day of prednisone or prednisone-equivalent within past 4
             weeks

          -  RA disease duration (from symptom onset) of more than 6 months

          -  Having clinical disease activity index (CDAI) of >2.8 but ≤22 (i.e., either low or
             moderate disease activity), within 30 days of study enrollment

        Exclusion Criteria:

          -  Aged <18 years

          -  Pregnant women

          -  Known personal history of CVD (clinical diagnoses of stroke, transient ischemic
             attack, myocardial infarction, acute coronary syndrome, peripheral arterial disease,
             percutaneous coronary intervention or coronary bypass graft surgery)

          -  Use of high-dose statins (e.g., atorvastatin 40-80 mg/day or rosuvastatin 20-40
             mg/day) currently or within past 3 months, or any dose changes of statins or of blood
             pressure medications that may affect endothelial function (i.e.,
             angiotensin-converting-enzyme [ACE] inhibitors or angiotensin receptor blockers
             [ARBs]) within past 3 months. If on statin or an ACE-I or ARB, there should be no
             anticipated dose changes over the next 6 months.

          -  Persons with intra-cardiac and intra-pulmonary shunts, unstable cardiopulmonary
             conditions, or anyone on chronic oxygen therapy

          -  Persons taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl
             trinitrate (nitroglycerin), sodium nitroprusside, amyl nitrite ("poppers")

          -  Severe hepatic impairment (liver function tests >1.5 times upper limit of normal)
             within past 4 weeks

          -  Severe impairment in renal function (serum creatinine ≥1.5 mg/dL) within past 4 weeks

          -  Hypotension (defined as blood pressure [BP] <90/60)

          -  Hereditary degenerative retinal disorders (including genetic disorders of retinal
             phosphodiesterases)

          -  Persons already taking (or taken within 3 months) sildenafil or other PDE inhibitors
             (i.e., tadalafil, vardenafil)

          -  Persons unable to provide voluntary written informed consent

          -  Severe hypertension (BP >170/110)

          -  Persons with HIV/AIDS