The Effect of Inhaled Nitric Oxide on Deadspace in COPD

NCT04069052 | Completed Early Phase 1

• 1 other identifier: DMED-2274-19
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Dyspnea; Exertional Dyspnea; Dead Space; Exercise; Inspiratory Neural Drive

Outcome Measures

Primary Outcomes (2)

• Dyspnea Intensity

  Primary objective is to measure perceptual (e.g. intensity of dyspnea and leg discomfort) responses at isotime (maximum exercise time achieved by all participants) during a standardized cardiopulmonary exercise testing (cycle ergometer).

  At 4 minutes from start of exercise

• Inspiratory neural drive

  Primary objective is to measure inspiratory neural drive (IND) by diaphragm activation (EMGdi/EMGdi max) at isotime (maximum exercise time achieved by all participants) during cardiopulmonary exercise testing (cycle ergometer).

  At 4 minutes from start of exercise

Secondary Outcomes (5)

• Lung volumes

  At 4 minutes from start of exercise

• Trans-diaphragmatic Pressure (Pdi)

  At 4 minutes from start of exercise

• Gastric Pressure (Pga)

  At 4 minutes from start of exercise

• Esophageal Pressure (Pes)

  At 4 minutes from start of exercise

• Metabolic and gas exchange

  At 4 minutes from start of exercise

Study Arms (2)

Inhaled Nitric Oxide

EXPERIMENTAL

Inhaled nitric oxide administered throughout 4 min exercise protocol at 800 ppm.

Drug: Nitric Oxide

Placebo

PLACEBO COMPARATOR

Inhaled room air administered throughout 4 min exercise protocol at FiO2 = 0.21.

Drug: Placebo

Interventions

Nitric Oxide DRUG

Gaseous pulmonary vasodilator, SoKinox (nitric oxide) flowed into a mask and breathed in.

Also known as: SoKinox

Inhaled Nitric Oxide

Placebo DRUG

Room air (placebo) flowed into a mask and breathed in.

Also known as: Room air

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• current or ex-smokers (\>=20 pack-years)
• male or female \>45 years of age
• mild COPD as defined by Medical Research Council dyspnea scale \>=3 and post-bronchodilator FEV1 \>=80% predicted and FEV1/FVC \<0.7 and \<LLN
• ability to perform all study procedures and provide/sign informed consent

You may not qualify if:

• women of childbearing age who are pregnant or trying to become pregnant
• active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation
• important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
• use of daytime oxygen, or exercise-induced O2 desaturation to \<80% on room air
• body mass index (BMI) \<18.5 or =\>35.0 kg/m2
• echocardiographic evidence of pulmonary hypertension
• prior history of pulmonary thromboembolism or systemic vasculopathy

Sponsors & Collaborators

• Dr. Denis O'Donnell: lead

Study Sites (1)

Respiratory Investigation Unit, Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea; Motor Activity

Interventions

Nitric Oxide

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; Behavior

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Denis E O'Donnell, MD

  Queen's University, Respiratory Investigation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single-centre, double-blinded, crossover study

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: August 28, 2019
• Study Start: September 1, 2021
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)