Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?

• Status: Terminated
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kimberly Liang; University of Pittsburgh
• Treatments: Sildenafil Citrate

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