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Mechanisms of Exertional Dyspnea in Fibrotic Interstitial Lung Disease (Dyspnea_ILD)

This study is not yet open for participant recruitment.
Verified April 2013 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01781793
First received: January 28, 2013
Last updated: April 3, 2013
Last verified: April 2013
History of Changes
  Purpose

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 mechanism by which hyperoxia improves 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). The secondary hypothesis is that experimental reduction of neuromechanical uncoupling via hyperoxic breathing will reduce exertional dyspnea and improve exercise endurance. The tertiary hypothesis is that healthy controls, compared to ILD participants, will have significantly less dyspnea and neuromechanical uncoupling with a lower work of breathing and a less pronounced physiological and sensory response to hyperoxia.


Condition Intervention
Lung; Disease, Interstitial, With Fibrosis
Healthy
 Other: Room air (21% oxygen)
Other: Hyperoxia (60% oxygen)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Supportive Care
Official Title: Mechanisms of Exertional Dyspnea in Fibrotic Interstitial Lung Disease

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • To determine the physiological mechanisms of exertional dyspnea in patients with fibrotic ILD [ Time Frame: Paramters 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. ] [ Designated as safety issue: No ]
    Included will be 35 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. 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).


Secondary Outcome Measures:
  • To determine the mechanism by which hyperoxia improves exertional dyspnea and exercise time [ Time Frame: Paramters 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. ] [ Designated as safety issue: No ]
    Patients will perform a cross-over study with two symptom-limited constant-load cycle exercise tests on separate days at an intensity corresponding to 75% of their peak incremental work rate. These tests will be performed while breathing room air on one visit and hyperoxia (60% oxygen) on the other. Detailed physiological and sensory measurements will be performed and used for the primary outcome measure. Multivariate linear regression will be used to identify the association of improvement in neuromechanical uncoupling (and its individual components) with improvement of both exertional dyspnea and exercise time.

  • To determine any physiological mechanistic differences of exertional dyspnea between participants with fibrotic ILD and healthy control participants. [ Time Frame: Paramters 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. ] [ Designated as safety issue: No ]
    Control participants will undergo the same exercise and physiological testing as the fibrotic ILD participants and comparisons between the 2 groups will be made.


Estimated Enrollment: 70
Study Start Date: June 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fibrotic ILD Patient
To compare the effects of neuromechanical uncoupling, exertional dyspnea, and exercise endurance in Fibrotic ILD patients breathing room air (21% oxygen) during a constant work rate exercise test compared to the same constant work rate exercise test breathing hyperoxia (60% oxygen). The two exercise tests are separated by a minimum of 48 hours.
 Other: Room air (21% oxygen)
humidified room air will be inspired
Other: Hyperoxia (60% oxygen)
humidified hyperoxia (60% oxygen) will be inspired
Active Comparator: Healthy Control Participant
To compare the effects of neuromechanical uncoupling, exertional dyspnea, and exercise endurance in healthy control participants breathing room air (21% oxygen) during a constant work rate exercise test compared to the same constant work rate exercise test breathing hyperoxia (60% oxygen). The two exercise tests are separated by a minimum of 48 hours.
 Other: Room air (21% oxygen)
humidified room air will be inspired
Other: Hyperoxia (60% oxygen)
humidified hyperoxia (60% oxygen) will be inspired

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria - Fibrotic ILD participants:

  • 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

Exclusion Criteria - Fibrotic ILD Participants:

  • 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

Inclusion criteria - healthy controls:

  • healthy
  • between 40-80 years of age (inclusive)

Exclusion criteria - healthy controls:

  • currently smoking or smoked more than 20 packs per year in the past
  • possess any disease that limits exercise capacity 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01781793

Contacts
Contact: Sabrina S Wilkie, MSc 604.806.8835 sabrina.wilkie@hli.ubc.ca

Locations
Canada, British Columbia
UBC James Hogg Research Centre, St. Paul's Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6Z1Y6
Principal Investigator: Jordan A Guenette, PhD            
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Jordan A Guenette, PhD UBC James Hogg Research Centre
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01781793     History of Changes
Other Study ID Numbers: Dyspnea ILD
Study First Received: January 28, 2013
Last Updated: April 3, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
dyspnea, exercise endurance, lung disease

Additional relevant MeSH terms:
Dyspnea
Fibrosis
Lung Diseases
Pulmonary Fibrosis
Lung Diseases, Interstitial
 Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013