Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?

NCT02908490 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: PRO14120209
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arthritis, Rheumatoid; Atherosclerosis

Keywords

Arthritis, Rheumatoid; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Brachial Artery Flow Mediated Dilation (FMD) Without Nitroglycerin at 3 Months

  The methods of assessment of endothelial function via FMD will be performed following guidelines. Using Duplex ultrasound with a high-resolution linear array transducer, the difference between the maximum brachial artery diameter (BAD) postocclusion and the baseline diameter will be calculated, expressed as a percentage (%BAD). Generally, %BAD values below 5-7% represent endothelial dysfunction, which is associated with CV risk factors, future CVD and mortality.

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Secondary Outcomes (14)

• Change From Baseline in Peripheral Arterial Tone (PAT) LnRHI at 3 Months

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

• Change From Baseline in hsCRP at 3 Months

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

• Change From Baseline in ESR at 3 Months

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

• Change From Baseline in Number of Participants With Detectable IL-6 at 3 Months

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

• Change From Baseline in RF at 3 Months

  Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Study Arms (2)

Initial Sildenafil

EXPERIMENTAL

Sildenafil 50 mg orally once daily for first 3 months, then after 2-week washout, Placebo orally once daily for 3 months

Drug: Sildenafil; Other: Placebo

Initial Placebo

PLACEBO COMPARATOR

Placebo orally once daily for first 3 months, then after 2-week washout, Sildenafil 50 mg orally once daily for 3 months

Drug: Sildenafil; Other: Placebo

Interventions

Sildenafil DRUG

Sildenafil 50 mg once daily

Also known as: Viagra, Revatio

Initial Placebo; Initial Sildenafil

Placebo OTHER

Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill

Initial Placebo; Initial Sildenafil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets 2010 American College of Rheumatology (ACR) classification criteria for diagnosis of RA
• Aged 18 years or older

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Kimberly Liang: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Atherosclerosis

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Kimberly P. Liang, MD, MS
• Organization: University of Pittsburgh

liangkp@upmc.edu

412-586-3550

Study Officials

• Kimberly P Liang, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: September 21, 2016
• Study Start: April 1, 2017
• Primary Completion: June 4, 2020
• Study Completion: December 31, 2020
• Last Updated: August 13, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)