Recruiting
Phase 2

Sildenafil

Sponsor:

University of Alberta

Code:

NCT05061368

Conditions

Chronic Obstructive Pulmonary Disease

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Accepted

Interventions

Sildenafil Citrate

Placebo

Study Details

Brief summary:

Chronic obstructive pulmonary disease (COPD) is a condition characterized by airway obstruction. Patients with COPD experience significant shortness of breath on exertion. The mechanisms responsible for shortness of breath on exertion are well understood in moderate and severe COPD, but, are poorly understood in mild COPD where symptoms appear disproportionate to the degree of airway obstruction.

Mild COPD patients show an exaggerated breathing response to exercise, determined by the breathing response to carbon dioxide production (V̇E/V̇CO2). Recent work suggests that the increased V̇E/V̇CO2 during exercise in mild COPD is secondary to increased deadspace (i.e. lung regions with ventilation but no perfusion) and/or ventilation/perfusion (V̇A/Q) inequality (poor matching of ventilation to perfusion). Researchers have proposed that the increased deadspace or V̇A/Q inequality is secondary to pulmonary vascular dysfunction and hypoperfusion of the pulmonary capillaries.

Recently, we have shown that inhaled nitric oxide, a potent dilator of pulmonary vasculature, reduces shortness of breath and V̇E/V̇CO2, and improves exercise capacity in mild COPD. This preliminary finding suggests that pulmonary vascular dysfunction is an important contributor to exercise intolerance in mild COPD. Here, we aim to test whether sildenafil, an oral pulmonary vasodilator, can improve exercise tolerance and shortness of breath in mild COPD.

Conditions

Chronic Obstructive Pulmonary Disease

Study ID

NCT05061368

Start date

Mar 1, 2022

Status verified date

Jul, 2026

Completion date

May, 2027

Anticipated

Primary completion date

May, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

Participants will have COPD as defined as:

1. Post bronchodilator Forced Expiratory Volume in one second (FEV1) to Forced Vital Capacity (FVC) ratio (FEV1/FVC) below the lower limit of normal
2. FEV1 >30% of predicted (lower limit of GOLD severe COPD classification)

COPD Free Controls will have:

1. No diagnosis of COPD
2. Post bronchodilator Forced Expiratory Volume in one second (FEV1) to Forced Vital Capacity (FVC) ratio (FEV1/FVC) above the lower limit of normal
3. FEV1 >80% of predicted

Exclusion Criteria:

1. Absolute contraindication to exercise testing or an orthopedic condition that may limit exercise testing.
2. Pre-existing cardiac conditions (heart failure, congenital heart defect, valvular disease) that may limit exercise testing
3. A diagnosis of pulmonary hypertension preceding COPD
4. Current phosphodiesterase type-5 inhibitor, nitrate, opioid, azole antifungal, macrolide antibiotic, protease inhibitor, alpha blocker, riociguat, mifepristone or rifamycin use.
5. Pregnancy or lactation.
6. Women of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy throughout the study. Acceptable methods of contraception include tubal ligation, oral contraceptive, barrier methods (intra-uterine device, diaphragm, female condom, male condom). Abstinence is an acceptable form of contraception, only insofar as patients agree to use another acceptable method of birth control, preferably a barrier method, if they become sexually active.
7. Postmenopausal female participants must be amenorrheic for ≥12 months.

Study Design

Enrollment

160 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sildenafil

Participants will be administered a 25 mg oral dose of sildenafil.

placebo comparator: Placebo

Participants will be administered an oral placebo indistinguishable from the sildenafil pill.

Interventions

Sildenafil Citrate

Phosphodiesterase Type 5 inhibitor. Known to potentiate nitric oxide mediated vasodilation.

Placebo

Placebo

Primary outcome measure

  • Exercise Capacity [ Time Frame: Within 20-25 minutes post-dose ]

Central Contacts and Locations

Central contacts

Desi Fuhr, MSc

7804921121fuhr@ualberta.ca

Rhys Beaudry, Ph.D.

7804928027rhys.beaudry@ualberta.ca

Locations

Clinical Physiology Laboratory

Recruiting

Edmonton, Alberta, Canada, T6G2R3

Contacts

Desi Fuhr, MSc

780-492-1121fuhr@ualberta.ca

Michael K Stickland, PhD

780-492-3995michael.stickland@ualberta.ca

More Information

Sponsor

University of Alberta

Last update posted

Jul 8, 2026

Last verified

Jul, 2026

Keywords

  • COPD
  • Sildenafil
  • Pulmonary Vascular Function
  • Pulmonary Vascular Pressure
  • DLCO
  • Pulmonary Capillary Blood Volume
  • Dyspnea
  • Exercise Tolerance
  • Peak Oxygen Uptake
  • Cardiopulmonary Fitness

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Alberta on 2026-07-08.