The Effect of Inhaled Nitric Oxide (iNO) on Physiologic Dead Space in Patients With Mild Chronic Obstructive Pulmonary Disease

DMED-2274-19

Chronic obstructive pulmonary disease (COPD) is a progressive disease of the respiratory system that generally develops as a result of smoking. Most people with COPD are classified as having "mild" disease severity and may not have significantly impaired lung function (e.g. flow) as measured by traditional lung function tests. However, multiple studies have shown that patients with mild disease already have significant damage to the small airways and blood vessels of the pulmonary system. This results in a considerable portion of the lung that does not participate in gas exchange, a phenomenon called physiologic dead space. Mild COPD patients develop symptoms of intolerable breathlessness early in exercise compared with healthy individuals. Previous studies have shown that pulmonary vasodilators, which locally increase blood vessel radius, may improve gas exchange and reduce symptoms of breathlessness in patients with mild COPD. Therefore, the objective of this study is to determine the effect of reducing dead space with a pulmonary vasodilator on the intensity of breathlessness during exercise in patients with mild COPD. This five visit, double-blinded, placebo-controlled crossover study will test the impact of inhaled nitric oxide, a direct vasodilator, during cardiopulmonary exercise on dead space and breathlessness intensity. Use of an esophageal catheter during testing will additionally permit measurement of neural drive to breathe and pulmonary mechanics throughout the protocol. Though patients with mild COPD represent the majority of the COPD population, their symptoms remain poorly managed by current, inefficient standard of care. The proposed study will examine dead space reduction as a novel therapeutic target for improving breathlessness and exercise tolerance in patients with mild COPD.

2021-09-01

2023-05-30

2023-05-30

Completed

Early phase I

13

Inclusion Criteria: 1. clinically stable as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admission in the preceeding 6 weeks 2. current or ex-smokers (\>=20 pack-years) 3. male or female \>45 years of age 4. mild COPD as defined by Medical Research Council dyspnea scale \>=3 and post-bronchodilator FEV1 \>=80% predicted and FEV1/FVC \<0.7 and \<LLN 5. ability to perform all study procedures and provide/sign informed consent Exclusion Criteria: 1. women of childbearing age who are pregnant or trying to become pregnant 2. active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation 3. important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s) 4. use of daytime oxygen, or exercise-induced O2 desaturation to \<80% on room air 5. body mass index (BMI) \<18.5 or =\>35.0 kg/m2 6. echocardiographic evidence of pulmonary hypertension 7. prior history of pulmonary thromboembolism or systemic vasculopathy

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2024-04-03