Pulmonary Gas Exchange and Neuro-sensory Abnormalities in Patients With Idiopathic Pulmonary Fibrosis and Mild Mechanical Restriction. Implications for Dyspnea and Exercise Intolerance

DMED 2495-21

Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease marked by reduced exercise capacity and activity-related breathlessness (commonly termed dyspnea). Our previous work has shown that dyspnea during exercise is associated with an increased drive to breathe (inspiratory neural drive; IND). However, little work has been done to understand the mechanisms of exertional dyspnea in patients with mild IPF. The objectives of this study are to compare the acute effects of inhaled nitric oxide to placebo on ventilatory efficiency (VE/VCO2), and IND at rest and during a standard cardiopulmonary exercise test (CPET). Twenty patients with diagnosed IPF with mild (or absent) mechanical restriction and 20 healthy age- and sex-matched controls will be recruited from a database of volunteers and from the Interstitial Lung Disease and Respirology clinics at Hotel Dieu Hospital. Participants with cardiovascular, or any other condition that contributes to dyspnea or abnormal cardiopulmonary responses to exercise will be excluded. After giving written informed consent, all participants will complete 7 visits, conducted 2 to 7 days apart. Visit 1 (screening): medical history, pulmonary function testing and a symptom limited incremental CPET. Visit 2: Standard CT examination conducted at KGH Imaging. Visit 3: assessment of resting chemoreceptor sensitivity, followed by a symptom limited incremental CPET to determine peak work rate (Wmax). Visits 4 \& 5 (run-in): familiarization to standardized constant work rate (CWR) CPET to symptom limitation at 75% Wmax. Visits 6 \& 7 (Randomized \& Blinded): CWR CPET to symptom limitation while breathing a gas mixture with either 1) 40 ppm iNO or 2) placebo \[medical grade normoxic gas, 21% oxygen\]. The proposed work has the potential to provide important physiological insights into the underlying mechanisms of heightened dyspnea, as well as examine therapeutic avenues to improve quality of life in patients with IPF.

2022-04-21

2024-12-30

2025-02-28

Recruiting

Early phase I

40

Inclusion criteria: * clinically stable, as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admissions in the preceding 6 weeks; * Mild or absent mechanical restriction as determined by a total lung capacity (TLC) \>70% predicted; * male or female non-pregnant adults \>40 years of age; * ability to perform all study procedures and provide informed consent. * A key IPF inclusion criterion includes, in addition to the above, a clinical diagnosis of idiopathic pulmonary fibrosis. Exclusion criteria: * women of childbearing potential who are pregnant or trying to become pregnant; * computed tomography evidence of any (significant) emphysema * evidence of airway obstruction (forced expiratory volume in 1 s/forced vital capacity \<0.70, * active cardiopulmonary disease (other than IPF) or other comorbidities that could contribute to dyspnea and exercise limitation; * history/clinical evidence of asthma, atopy and/or nasal polyps; * currently taking phosphodiesterase type 5 inhibitors; * important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s); * body mass index (BMI) \<18.5 or ≥35.0 kg/m2; * use of daytime oxygen or exercise-induced O2 desaturation (\<80% on room air).

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2024-04-03