Mechanisms of Exertional Dyspnea in Fibrotic Interstitial Lung Disease

NCT01781793 | Completed

• 1 other identifier: H13-00059
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Exertional dyspnea is a major source of crippling distress and is the hallmark symptom of fibrotic interstitial lung disease (ILD). Due to the scientific community's poor understanding of the pathophysiological mechanisms of dyspnea there are no therapeutic interventions that consistently reduce dyspnea in this population. The investigators aim to determine the physiological mechanisms of exertional dyspnea in patients with fibrotic ILD and the impact of hyperoxia on exertional dyspnea and exercise endurance. This study will likely identify an important physiological mechanism of dyspnea in fibrotic ILD and may contribute to the development of effective therapies to reduce dyspnea in this population. The central hypothesis is that dyspnea in fibrotic ILD is primarily a result of an imbalance between the drive to breathe and the tidal volume response of the respiratory system (i.e., neuromechanical uncoupling) and that experimental reduction of neuromechanical uncoupling via hyperoxic breathing will reduce exertional dyspnea and improve exercise endurance.

Conditions

Lung; Disease, Interstitial, With Fibrosis

Keywords

dyspnea, exercise endurance, lung disease

Outcome Measures

Primary Outcomes (1)

• To determine the physiological mechanisms of exertional dyspnea (Aim 1) and the effects of hyperoxia on dyspnea and cycle endurance in patients with fibrotic ILD (Aim 2)

  Included will be 16 patients with fibrotic ILD who have no other pulmonary or extra-pulmonary limitation to exercise. Patients will perform an incremental symptom-limited cardio-pulmonary exercise test while detailed ventilatory, metabolic, respiratory mechanical, neuromechanical and sensory responses are measured. Patients will perform a cross-over study with two symptom-limited constant-load cycle exercise tests on separate days at 75% of peak incremental work rate. These tests will be performed breathing room air on one visit and hyperoxia on the other. Detailed physiological and sensory responses will be measured. Multivariate linear regression will be used to identify the association between neuromechanical uncoupling and exertional dyspnea, adjusting for the individual components of neuromechanical uncoupling (i.e., drive to breathe and tidal volume response) (Aim 1). Paired t-tests will be used to compare outcomes between room air and hyperoxic tests (Aim 2).

  Parameters will be measured during the four visits. Each visit is separated by at least 48 hours and all visits will be completed within 8 weeks. During the course of each visit, parameters will be measured at rest and during the exercise intervention.

Secondary Outcomes (1)

• To determine the mechanism by which hyperoxia improves exertional dyspnea and exercise time

  Parameters will be measured during the four visits. Each visit is separated by at least 48 hours and all visits will be completed within 8 weeks. During the course of each visit, parameters will be measured at rest and during the exercise intervention.

Study Arms (2)

Fibrotic ILD Patients, Room Air

PLACEBO COMPARATOR

Fibrotic ILD patients will breathe room air (21% oxygen) during a constant work rate exercise test

Other: Room air

Fibrotic ILD Patients, Hyperoxia

ACTIVE COMPARATOR

Fibrotic ILD patients will breathe hyperoxia (60% oxygen) during a constant work rate exercise test

Other: Hyperoxia

Interventions

Room air OTHER

Humidified room air (21% oxygen) will be inspired

Fibrotic ILD Patients, Room Air

Hyperoxia OTHER

60% oxygen will be inspired

Fibrotic ILD Patients, Hyperoxia

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF), idiopathic fibrotic non-specific interstitial pneumonia (NSIP), chronic hypersensitivity pneumonitis (HP), or unclassifiable interstitial lung disease (ILD) with a differential diagnosis that consists of the above diagnoses
• Fibrosis on high resolution computed tomography (HRCT): honeycombing, reticulation, or traction bronchiectasis
• Oxygen saturation ≥ 92% by pulse oximetry at rest while breathing room air

You may not qualify if:

• Concurrent participation in or recent completion (less than 6 weeks) of pulmonary rehabilitation
• A significant lung disease other than fibrotic ILD that, based on clinical assessment, could impair your ability to exercise
• Significant emphysema
• Pulmonary hypertension (high blood pressure in your lungs' arteries)
• Prednisone (a corticosteroid medication) in excess of 10mg/day for at least two weeks within three months of the first study visit
• An ulcer or tumor in your esophagus, or a nasal septum deviation
• Had recent nasopharyngeal surgery
• A cardiac pacemaker
• Allergies to latex and sensitivities to local anaesthetics
• Current smokers or smoked more than 20 packs per year in the past

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

UBC James Hogg Research Centre, St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Related Publications (1)

• Schaeffer MR, Ryerson CJ, Ramsook AH, Molgat-Seon Y, Wilkie SS, Dhillon SS, Mitchell RA, Sheel AW, Khalil N, Camp PG, Guenette JA. Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease. Eur Respir J. 2017 May 25;49(5):1602494. doi: 10.1183/13993003.02494-2016. Print 2017 May. No abstract available.

  PMID: 28546272 DERIVED

MeSH Terms

Conditions

Disease; Dyspnea; Lung Diseases

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Officials

• Jordan A Guenette, PhD

  UBC James Hogg Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2013
• First Posted: February 1, 2013
• Study Start: September 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

CA (1)