Sildenafil Exercise: Role of PDE5 Inhibition

• Register: ClinicalTrials.gov
• Last refreshed on: 12 September 2022
• Main ID: NCT04039087
• Date of registration: 28/07/2019
• Prospective Registration: Yes
• Primary sponsor: National Jewish Health
• Public title: Sildenafil Exercise: Role of PDE5 Inhibition
• Scientific title: Mechanisms of Exercise Intolerance in Cystic Fibrosis: Role of PDE5 Inhibition
• Date of first enrolment: September 5, 2019
• Target sample size: 40
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04039087
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Supportive Care. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Nora H Murphy, BS

• Name: Jennifer Taylor-Cousar, MD, MSCS
• Affiliation: National Jewish Health

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmed diagnosis of cystic fibrosis (CF) based on the following criteria: Positive
sweat chloride concentration =60 milliequivalents (mEq)/liter (by pilocarpine
iontophoresis) and/or genotype with two identifiable disease-causing mutations
consistent with CF, and accompanied by one or more clinical features consistent with
the CF phenotype

- Male or female patients = 9 years of age

- forced expiratory volume at one second (FEV1) = 30% predicted and = 70% for patients =
18 years of age and = 80% for patients = 18 years of age

- Clinically stable without evidence of acute upper or lower respiratory tract infection
or current pulmonary exacerbation within the 14 days prior to the screening visit

- Resting oxygen saturation (room air) >85%

- Patients with or without CF related diabetes

- Ability to perform spirometry reproducibly (according to American Thoracic Society
criteria)

- Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled
antibiotics)

Exclusion Criteria:

- Children 8 yrs. old and younger

- Subjects who weigh < 20 Kgs

- History of hypersensitivity to sildenafil

- Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)

- Breastfeeding, pregnant, or verbal expression of unwillingness to practice an
acceptable birth control method (abstinence, hormonal or barrier methods, partner
sterilization or intrauterine device) during participation in the study for women of
child-bearing potential.

- History of significant hepatic disease (aspartate transaminase or alanine transaminase
> 3 times the upper limit of normal at screening, documented biliary cirrhosis, or
portal hypertension),

- History of significant cardiovascular disease (history of aortic stenosis, coronary
artery disease, or life-threatening arrhythmia),

- History of severe neurological disease (e.g. history of stroke),

- History of severe hematologic disease (e.g. history of bleeding diathesis; current
international normalized ratio (INR) > 2.0

- History of severe ophthalmologic disease (e.g. history of retinal impairment or
non-arteritic ischemic optic neuritis)

- History of severe renal impairment (creatinine >1.8 mg/dL.)

- Inability to swallow pills

- Previous organ transplantation

- Use of concomitant nitrates, a-blocker, or Ca channel blocker (currently or within one
month of Visit 1)

- Use of concomitant medications known to be potent inhibitors of CYP3A4 [e.g.
ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin
(currently or within one month of initiation of study drug)] (NOTE: use of
azithromycin is NOT a cause for exclusion)

- History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacteria
massiliense within 2 years of screening

- History of migraine headaches.

- Presence of a condition or abnormality that in the opinion of the investigator would
compromise the safety of the subject or the quality of the data

- Initiation of a cystic fibrosis transmembrane conductance regulator (CFTR) modulator
therapy less than 1 month prior to first dose of sildenafil or placebo

- Use of anticoagulants

- Frank pulmonary hypertension[right ventricular systolic pressure (RVSP) >40 mm Hg by
echocardiography)

- History of Priapism or known penile anatomical deformities



Age minimum: 9 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Sildenafil 40mg oral capsule

Drug: Placebo Oral capsule

Primary Outcome(s)

6 Minute Walk Distance (6MWD) [Time Frame: Change in distance walked between week 1 and week 12.]

Secondary Outcome(s)

Flow-Mediated Dilation (FMD) [Time Frame: Change in FMD between weeks 1 and 12]

CFQ-R respiratory domain score [Time Frame: Quality of life assessed at weeks 1 and 12.]

Cardiac strain [Time Frame: Change in cardiac strain between weeks 1 and 12]

Skeletal muscle function [Time Frame: Change in skeletal muscle function between weeks 1 and 12]

Secondary ID(s)

Sildenafil Exercise

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Augusta University

Cystic Fibrosis Foundation