Oral Sildenafil for Exercise Capacity, Dyspnea and Cardiopulmonary Function in COPD

NCT05061368 | Recruiting Phase 2

• 1 other identifier: Pro00108944
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Exercise Capacity

  Maximal oxygen uptake (peak VO2)

  Within 20-25 minutes post-dose

Secondary Outcomes (4)

• Dyspnea during exercise

  Assessed every 2-minutes until completion of the exercise trial

• Pulmonary function during exercise

  Within 20-25 minutes post-dose

• Cardiac Output during exercise

  Within 20-25 minutes post-dose

• Pulmonary Artery Systolic Pressure

  Assessed for five consecutive cardiac cycles and are measured in triplicate

Study Arms (2)

Sildenafil

EXPERIMENTAL

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

Drug: Sildenafil Citrate

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Placebo OTHER

Placebo

Placebo

Sildenafil Citrate DRUG

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

Sildenafil

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will have COPD as defined as:
• Post bronchodilator Forced Expiratory Volume in one second (FEV1) to Forced Vital Capacity (FVC) ratio (FEV1/FVC) below the lower limit of normal
• FEV1 \>30% of predicted (lower limit of GOLD severe COPD classification)
• COPD Free Controls will have:
• No diagnosis of COPD
• Post bronchodilator Forced Expiratory Volume in one second (FEV1) to Forced Vital Capacity (FVC) ratio (FEV1/FVC) above the lower limit of normal
• FEV1 \>80% of predicted

You may not qualify if:

• Absolute contraindication to exercise testing or an orthopedic condition that may limit exercise testing.
• Pre-existing cardiac conditions (heart failure, congenital heart defect, valvular disease) that may limit exercise testing
• A diagnosis of pulmonary hypertension preceding COPD
• Current phosphodiesterase type-5 inhibitor, nitrate, opioid, azole antifungal, macrolide antibiotic, protease inhibitor, alpha blocker, riociguat, mifepristone or rifamycin use.
• Pregnancy or lactation.
• 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.
• Postmenopausal female participants must be amenorrheic for ≥12 months.

Sponsors & Collaborators

• University of Alberta: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Clinical Physiology Laboratory

Edmonton, Alberta, T6G2R3, Canada

RECRUITING

Related Publications (4)

• Blanco I, Gimeno E, Munoz PA, Pizarro S, Gistau C, Rodriguez-Roisin R, Roca J, Barbera JA. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med. 2010 Feb 1;181(3):270-8. doi: 10.1164/rccm.200907-0988OC. Epub 2009 Oct 29.

  PMID: 19875684 BACKGROUND

• Phillips DB, Brotto AR, Ross BA, Bryan TL, Wong EYL, Meah VL, Fuhr DP, van Diepen S, Stickland MK; Canadian Respiratory Research Network. Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized-control cross-over trial. J Physiol. 2021 Mar;599(5):1665-1683. doi: 10.1113/JP280913. Epub 2021 Jan 25.

  PMID: 33428233 BACKGROUND

• Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010.

  PMID: 16291984 BACKGROUND

• Blanco I, Santos S, Gea J, Guell R, Torres F, Gimeno-Santos E, Rodriguez DA, Vilaro J, Gomez B, Roca J, Barbera JA. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur Respir J. 2013 Oct;42(4):982-92. doi: 10.1183/09031936.00176312. Epub 2013 Feb 21.

  PMID: 23429918 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

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

Study Officials

• Michael K Stickland, Ph.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Desi Fuhr, MSc

CONTACT

7804921121; fuhr@ualberta.ca

Rhys Beaudry, Ph.D.

CONTACT

7804928027; rhys.beaudry@ualberta.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blinded: participants, investigators and outcome assessors are blinded to condition until data entry and analysis are completed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double Blinded, Placebo Controlled Repeated Measures

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: September 29, 2021
• Study Start: March 1, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)