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Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea

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ClinicalTrials.gov Identifier: NCT03018756
Recruitment Status : Suspended (Temporarily suspended due to COVID-19)
First Posted : January 12, 2017
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Dr. Denis O'Donnell, Queen's University

Tracking Information
First Submitted Date  ICMJE December 20, 2016
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE January 2017
Actual Primary Completion Date June 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle ergometer exercise [ Time Frame: 10-minutes post-treatment ]
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (4-minutes) in both post-treatment constant-load cycle ergometer tests.
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (4-minutes) in both post-treatment constant-load treadmill tests.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
  • Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise [ Time Frame: 10-minutes post-treatment ]
    EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
  • Ventilation at a standardized time during cycle exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
  • Breathing frequency at a standardized time during cycle exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
  • Tidal volume at a standardized time during cycle exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
  • Inspiratory capacity at a standardized time during cycle exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
  • Diaphragm electromyography (EMGdi) at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
    EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (4-minutes) during both post-treatment constant-load treadmill tests.
  • Ventilation at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load treadmill tests.
  • Breathing frequency at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load treadmill tests.
  • Tidal volume at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load treadmill tests.
  • Inspiratory capacity at a standardized time during treadmill exercise [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load treadmill tests.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea
Official Title  ICMJE Use of Nebulized Fentanyl in Patients With Mild-to-Moderate Interstitial Lung Disease and Chronic Dyspnea
Brief Summary Patients with interstitial lung disease (ILD) experience distressing activity-related respiratory discomfort which is challenging to manage therapeutically. Interventions such as pulmonary rehabilitation, collaborative self-management, supplemental oxygen therapy and oral opiate medications, are variably effective and therapeutic responses to each in individual patients are difficult to predict. The purpose of this study is to evaluate the acute effects of inhaled opiate therapy (fentanyl citrate) on breathing discomfort (dyspnea) in individuals with mild-to-moderate ILD, as well as examine the potential mechanisms of dyspnea relief.
Detailed Description Treatment with opioids can improve activity related dyspnea by reducing central respiratory neural drive. Inhaled fentanyl citrate is an opioid that is generally well tolerated and has been shown to effectively relieve respiratory discomfort without causing systemic side-effects, although its mechanism of action are poorly understood. Based on the current evidence, non-sedating, rapidly active inhaled fentanyl represents a possible alternative and effective treatment of severe dyspnea in patients with ILD who require urgent treatment. As such, the primary objective of this study is to examine the acute effects of nebulized fentanyl on dyspnea intensity and quality in patients with mild-to-moderate ILD, as well as examine the neurophysiological mechanisms of dyspnea relief during fentanyl inhalation. It is believed that fentanyl when compared with placebo, will reduce inspiratory neural drive to the diaphragm and breathing frequency, resulting in improvements in dyspnea intensity during physical exertion. Alternatively, dyspnea relief after inhaled fentanyl may be independent of changes in neural drive, and instead linked to the presence of opioid receptors in the lungs that modulate afferent inputs to the brain, thereby favourably influencing perceived dyspnea.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Interstitial Lung Disease
Intervention  ICMJE
  • Drug: Fentanyl Citrate
    100 mcg fentanyl citrate will be inhaled via nebulizer.
    Other Name: inhaled fentanyl
  • Drug: Placebo
    0.9% saline solution will be inhaled via nebulizer
    Other Name: normal saline
Study Arms  ICMJE
  • Active Comparator: Fentanyl Citrate
    Single dose, nebulized 100 mcg fentanyl citrate. This is a double-blind, placebo-controlled, two-period crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate to that of a placebo (0.9% saline). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and placebo at the second treatment visit, patients in the other arm will receive placebo first and fentanyl second.
    Intervention: Drug: Fentanyl Citrate
  • Placebo Comparator: Placebo
    Single dose, nebulized 0.9% saline solution. This is a double-blind, placebo-controlled, two-period crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate to that of a placebo (0.9% saline). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and placebo at the second treatment visit, patients in the other arm will receive placebo first and fentanyl second.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Actual Enrollment  ICMJE
 (submitted: May 11, 2020)
21
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2017)
20
Estimated Study Completion Date  ICMJE August 1, 2022
Actual Primary Completion Date June 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fibrotic interstitial lung disease (ILD) diagnosis confirmed by specialty ILD clinic
  • A total lung capacity (TLC) <lower limit of normal and ≥60%predicted, a forced vital capacity (FVC) <lower limit of normal and ≥60%predicted, and a forced expiratory volume in 1 second (FEV1)/FVC >70%.
  • Clinically stable as defined by no changes in medication dosage or frequency of administration with no exacerbations or hospital admissions in the preceding 6 weeks.
  • Moderate-to-severe chronic activity related dyspnea as defined by a Baseline Dyspnea Index total score ≤9, modified Medical Research Council score >1, or oxygen cost diagram.
  • Ability to perform all study procedures and provide/sign informed consent.

Exclusion Criteria:

  • Women of childbearing age who are pregnant or trying to become pregnant.
  • Diffusing capacity of the lung for carbon monoxide (DLCO) <40 %predicted.
  • Presence of active cardiopulmonary disease other than ILD that could contribute to dyspnea and exercise limitation.
  • History of allergy or adverse reaction to fentanyl.
  • History of allergy or adverse reaction to latex
  • Presence of contraindications to pulmonary function or clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s).
  • Use of ambulatory oxygen or exercise-induced oxygen desaturation to < 80% on room air.
  • Body mass index (BMI) <18.5 or ≥35.0 kg/m2.
  • Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in the previous 2 weeks.
  • Use of opioid drugs (e.g., morphine, fentanyl, oxycodone, codeine, etc.) in the previous 4 weeks.

Note: Healthy volunteers will only be used to assist in the characterization of the IPF study group, i.e., for comparison of baseline exercise responses. They will not undergo treatment.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03018756
Other Study ID Numbers  ICMJE DMED-1921-16
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dr. Denis O'Donnell, Queen's University
Study Sponsor  ICMJE Queen's University
Collaborators  ICMJE Boehringer Ingelheim
Investigators  ICMJE
Principal Investigator: Denis E O'Donnell, MD, FRCPC Queen's University
PRS Account Queen's University
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP