Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?

• Register: ClinicalTrials.gov
• Last refreshed on: 22 February 2021
• Main ID: NCT02908490
• Date of registration: 08/07/2016
• Prospective Registration: Yes
• Primary sponsor: Kimberly Liang
• Public title: Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?
• Scientific title: Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?
• Date of first enrolment: April 1, 2017
• Target sample size: 26
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02908490
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Prevention. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Kimberly P Liang, MD
• Affiliation: University of Pittsburgh

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Atherosclerosis

Arthritis, Rheumatoid

Intervention(s)

Drug: Sildenafil

Other: Placebo

Primary Outcome(s)

Brachial Artery Flow Mediated Dilation (FMD) Without Nitroglycerin [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Secondary Outcome(s)

Adverse events (AE) related to treatment [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for autoimmunity-2 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Peripheral Arterial Tone (PAT) [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for inflammation-2 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for inflammation-3 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for endothelial dysfunction-4 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Serious adverse events (SAE) [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for atherosclerosis-2 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for endothelial dysfunction-1 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for atherosclerosis-3 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for atherosclerosis-1 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for autoimmunity-1 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for endothelial dysfunction-2 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for endothelial dysfunction-3 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Biomarkers for inflammation-1 [Time Frame: After 3 months of Sildenafil use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)]

Secondary ID(s)

PRO14120209

Source(s) of Monetary Support

Please refer to primary and secondary sponsors