<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03018756</url>
  </required_header>
  <id_info>
    <org_study_id>DMED-1921-16</org_study_id>
    <nct_id>NCT03018756</nct_id>
  </id_info>
  <brief_title>Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea</brief_title>
  <official_title>Use of Nebulized Fentanyl in Patients With Mild-to-Moderate Interstitial Lung Disease and Chronic Dyspnea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Queen's University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with interstitial lung disease (ILD) experience distressing activity-related&#xD;
      respiratory discomfort which is challenging to manage therapeutically. Interventions such as&#xD;
      pulmonary rehabilitation, collaborative self-management, supplemental oxygen therapy and oral&#xD;
      opiate medications, are variably effective and therapeutic responses to each in individual&#xD;
      patients are difficult to predict. The purpose of this study is to evaluate the acute effects&#xD;
      of inhaled opiate therapy (fentanyl citrate) on breathing discomfort (dyspnea) in individuals&#xD;
      with mild-to-moderate ILD, as well as examine the potential mechanisms of dyspnea relief.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment with opioids can improve activity related dyspnea by reducing central respiratory&#xD;
      neural drive. Inhaled fentanyl citrate is an opioid that is generally well tolerated and has&#xD;
      been shown to effectively relieve respiratory discomfort without causing systemic&#xD;
      side-effects, although its mechanism of action are poorly understood. Based on the current&#xD;
      evidence, non-sedating, rapidly active inhaled fentanyl represents a possible alternative and&#xD;
      effective treatment of severe dyspnea in patients with ILD who require urgent treatment. As&#xD;
      such, the primary objective of this study is to examine the acute effects of nebulized&#xD;
      fentanyl on dyspnea intensity and quality in patients with mild-to-moderate ILD, as well as&#xD;
      examine the neurophysiological mechanisms of dyspnea relief during fentanyl inhalation. It is&#xD;
      believed that fentanyl when compared with placebo, will reduce inspiratory neural drive to&#xD;
      the diaphragm and breathing frequency, resulting in improvements in dyspnea intensity during&#xD;
      physical exertion. Alternatively, dyspnea relief after inhaled fentanyl may be independent of&#xD;
      changes in neural drive, and instead linked to the presence of opioid receptors in the lungs&#xD;
      that modulate afferent inputs to the brain, thereby favourably influencing perceived dyspnea.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 25, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle ergometer exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>The 10-point Borg scale ranges from 0 &quot;nothing at all&quot; to 10 &quot;maximal/extremely strong&quot; 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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilation at a standardized time during cycle exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breathing frequency at a standardized time during cycle exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tidal volume at a standardized time during cycle exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inspiratory capacity at a standardized time during cycle exercise</measure>
    <time_frame>10-minutes post-treatment</time_frame>
    <description>Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Interstitial Lung Disease</condition>
  <arm_group>
    <arm_group_label>Fentanyl Citrate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Citrate</intervention_name>
    <description>100 mcg fentanyl citrate will be inhaled via nebulizer.</description>
    <arm_group_label>Fentanyl Citrate</arm_group_label>
    <other_name>inhaled fentanyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% saline solution will be inhaled via nebulizer</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fibrotic interstitial lung disease (ILD) diagnosis confirmed by specialty ILD clinic&#xD;
&#xD;
          -  A total lung capacity (TLC) &lt;lower limit of normal and ≥60%predicted, a forced vital&#xD;
             capacity (FVC) &lt;lower limit of normal and ≥60%predicted, and a forced expiratory&#xD;
             volume in 1 second (FEV1)/FVC &gt;70%.&#xD;
&#xD;
          -  Clinically stable as defined by no changes in medication dosage or frequency of&#xD;
             administration with no exacerbations or hospital admissions in the preceding 6 weeks.&#xD;
&#xD;
          -  Moderate-to-severe chronic activity related dyspnea as defined by a Baseline Dyspnea&#xD;
             Index total score ≤9, modified Medical Research Council score &gt;1, or oxygen cost&#xD;
             diagram.&#xD;
&#xD;
          -  Ability to perform all study procedures and provide/sign informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of childbearing age who are pregnant or trying to become pregnant.&#xD;
&#xD;
          -  Diffusing capacity of the lung for carbon monoxide (DLCO) &lt;40 %predicted.&#xD;
&#xD;
          -  Presence of active cardiopulmonary disease other than ILD that could contribute to&#xD;
             dyspnea and exercise limitation.&#xD;
&#xD;
          -  History of allergy or adverse reaction to fentanyl.&#xD;
&#xD;
          -  History of allergy or adverse reaction to latex&#xD;
&#xD;
          -  Presence of contraindications to pulmonary function or clinical exercise testing,&#xD;
             including inability to exercise because of neuromuscular or musculoskeletal&#xD;
             disease(s).&#xD;
&#xD;
          -  Use of ambulatory oxygen or exercise-induced oxygen desaturation to &lt; 80% on room air.&#xD;
&#xD;
          -  Body mass index (BMI) &lt;18.5 or ≥35.0 kg/m2.&#xD;
&#xD;
          -  Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake&#xD;
             inhibitors) in the previous 2 weeks.&#xD;
&#xD;
          -  Use of opioid drugs (e.g., morphine, fentanyl, oxycodone, codeine, etc.) in the&#xD;
             previous 4 weeks.&#xD;
&#xD;
        Note: Healthy volunteers will only be used to assist in the characterization of the IPF&#xD;
        study group, i.e., for comparison of baseline exercise responses. They will not undergo&#xD;
        treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Denis E O'Donnell, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen's University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Respiratory Investigation Unit, Queen's University</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>April 21, 2022</last_update_submitted>
  <last_update_submitted_qc>April 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Queen's University</investigator_affiliation>
    <investigator_full_name>Dr. Denis O'Donnell</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Dyspnea</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03018756
org study id: DMED-1921-16
nct id: NCT03018756
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle ergometer exercise
time frame: 10-minutes post-treatment
description: 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.
measure: Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise
time frame: 10-minutes post-treatment
description: 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.
measure: Ventilation at a standardized time during cycle exercise
time frame: 10-minutes post-treatment
description: Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
measure: Breathing frequency at a standardized time during cycle exercise
time frame: 10-minutes post-treatment
description: 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.
measure: Tidal volume at a standardized time during cycle exercise
time frame: 10-minutes post-treatment
description: Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
measure: Inspiratory capacity at a standardized time during cycle exercise
time frame: 10-minutes post-treatment
description: Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
arm group label: Fentanyl Citrate
arm group type: Active Comparator
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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 type: Drug
intervention name: Fentanyl Citrate
description: 100 mcg fentanyl citrate will be inhaled via nebulizer.
arm group label: Fentanyl Citrate
other name: inhaled fentanyl
intervention type: Drug
intervention name: Placebo
description: 0.9% saline solution will be inhaled via nebulizer
arm group label: Placebo
other name: normal saline
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Denis E O'Donnell, MD, FRCPC
role: Principal Investigator
affiliation: Queen's University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Queen's University
investigator full name: Dr. Denis O'Donnell
investigator title: Principal Investigator
mesh term: Lung Diseases
mesh term: Dyspnea
mesh term: Lung Diseases, Interstitial
mesh term: Fentanyl
sharing ipd: No