<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/NCT03824834</url>
  </required_header>
  <id_info>
    <org_study_id>MorEX_2019-5261</org_study_id>
    <nct_id>NCT03824834</nct_id>
  </id_info>
  <brief_title>Morphine to Maximize the Benefits of Exercise Training in COPD or ILD and Persistent Breathlessness</brief_title>
  <acronym>MorEx</acronym>
  <official_title>Morphine: a Novel Intervention to Maximize the Benefits of Exercise Training in Adults With Chronic Lung Disease and Persistent Breathlessness?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dennis Jensen, Ph.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the role of low-dose immediate-release oral morphine&#xD;
      as a novel adjunct pharmacotherapy to enable symptomatic adults with advanced chronic&#xD;
      obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) to exercise at higher&#xD;
      intensities for longer durations and maximize the psycho-physiological benefits of a&#xD;
      supervised exercise training program. We hypothesize that, compared to placebo, exercise&#xD;
      training with oral morphine will result in relatively greater improvements in exercise&#xD;
      endurance time and intensity ratings of perceived breathlessness during constant-load&#xD;
      cardiopulmonary cycle exercise testing (CPET) at 75% of peak power output (PPO).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Supervised exercise training programs (such as pulmonary rehabilitation) are an integral&#xD;
      component of the clinical management of COPD or ILD; a proven intervention for improving&#xD;
      symptom burden, quality of life, emotional function, exercise capacity, and risk of&#xD;
      hospitalization and death. While both low and high intensity exercise training benefits&#xD;
      adults with COPD or ILD, evidence supports that higher intensity exercise training produces&#xD;
      relatively greater physiological and symptomatic improvements. High intensity exercise of&#xD;
      adequate duration is, however, difficult and unpleasant for people with COPD or ILD due to&#xD;
      heightened exertional symptoms, particularly breathlessness.These symptoms persist despite&#xD;
      the patient's underlying disease being optimally managed according to evidence-based clinical&#xD;
      practice guideline standards.&#xD;
&#xD;
      Low-dose immediate-release oral morphine has recently shown promise as a novel adjunct&#xD;
      therapy to reduce exertional breathlessness and increase exercise endurance time in people&#xD;
      with advanced chronic lung disease (COPD). The purpose of this randomized, double-blind,&#xD;
      placebo-controlled, two-arm pilot study is to further explore the role of low-dose&#xD;
      immediate-release oral morphine as an adjunct pharmacotherapy to enable symptomatic adults&#xD;
      with advanced COPD or ILD to exercise at higher intensities for longer durations and maximize&#xD;
      the psycho-physiological benefits of a 5-week supervised exercise training program.&#xD;
&#xD;
      Adults with a clinical diagnosis of COPD or ILD and chronic breathlessness syndrome will be&#xD;
      randomized in a 1:1 ratio to exercise training with oral morphine (ExT+MOR) (n=20; 10 COPD&#xD;
      and 10 ILD) or exercise training with placebo (diluted simple syrup) (ExT+PLA) (n=20; 10 COPD&#xD;
      and 10 ILD). All eligible participants will complete four assessment visits (Visits 1, 2, 3&#xD;
      and 4) and 15 exercise training (T1-15) sessions. Assessment Visits 1 and 3 will include&#xD;
      post-bronchodilator (400 mg Salbutamol) pulmonary function testing and a symptom-limited&#xD;
      incremental cardiopulmonary exercise test (CPET) to determine peak power output (PPO). Visits&#xD;
      2 and 4 will include a symptom-limited constant-load CPET at 75% of the PPO determined at&#xD;
      Visit 1 and a dual energy x-ray absorptiometry (DEXA) scan to assess body composition.&#xD;
      Supervised exercise training will be performed three times per week for five weeks on an&#xD;
      electronically braked cycle ergometer, supervised by a trained exercise specialist. Exercise&#xD;
      sessions will be individualized based on participants' pre-defined PPO (initial intensity of&#xD;
      60% PPO), and progressed to ensure the participant is exercising at an intensity&#xD;
      corresponding to a breathlessness intensity rating of between 3-5 Borg 0-10 category ratio&#xD;
      scale (CR10) units and can complete at least 20-min of continuous cycling. Exercise duration&#xD;
      will be increased in 5-min intervals up to 40-min. Thereafter, exercise intensity will be&#xD;
      increased by 5-15% of baseline PPO.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 6, 2019</start_date>
  <completion_date type="Anticipated">November 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Study medications, both morphine sulphate and placebo, will be dispensed by the research pharmacist according to the patient's randomization assignment. Neither research staff, nor patients, nor the treating physicians will be aware of the treatment assignment before or after randomization.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiopulmonary exercise testing (CPET) endurance time</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Cardiopulmonary exercise testing (constant-load) will be used to assess change in endurance time pre to post intervention. Endurance time will be defined as the total duration of loaded pedalling (minutes).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Borg modified 0-10 category ratio scale (Borg CR10) for breathlessness intensity</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Borg modified 0-10 category ratio scale (Borg CR10) will be used to assess breathlessness intensity during constant-load CPET at isotime, defined as the highest equivalent 2-min interval of exercise completed by a given participant during each of the constant-load CPETs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short Form Health Survey (SF-36) for quality of life</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Short Form Health Survey (SF-36) will be used to assess change in quality of life pre to post intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multidimensional Dyspnoea Profile for 'usual' breathlessness</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Multidimensional Dyspnoea Profile will be used to assess change in 'usual' breathlessness pre to post intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression Scale (HADS) for anxiety and depressive symptoms</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Hospital Anxiety and Depression Scale (HADS) will be used to assess change in anxiety and depressive symptoms pre to post intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DEXA-derived body composition</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>DEXA will be used to assess change in fat free mass pre to post intervention. Fat free mass will be expressed as fat free mass index, which is the fat free mass per kg of total body weight per metre squared of standing height.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CPET physiological response (gas exchange)</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Breath-by-breath CPET (incremental) parameters will be averaged in 30-sec intervals at rest and during exercise. The change in peak volume of oxygen consumption pre to post will be reported.&#xD;
CPET parameters will be collected over the first 30-sec period of every second minute during exercise. Three main time points will be used to evaluate exercise test parameters: (1) pre-exercise rest, defined as the steady-state period after at least 3-min of breathing on the mouthpiece while seated at rest before exercise; (2) isotime (as defined above); and (3) peak exercise, defined as the average of the last 30-sec of loaded pedaling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CPET physiological response (power output)</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>Breath-by-breath CPET (incremental) parameters will be averaged in 30-sec intervals at rest and during exercise. The change in peak power output pre to post will be reported.&#xD;
CPET parameters will be collected over the first 30-sec period of every second minute during exercise. Three main time points will be used to evaluate exercise test parameters: (1) pre-exercise rest, defined as the steady-state period after at least 3-min of breathing on the mouthpiece while seated at rest before exercise; (2) isotime (as defined above); and (3) peak exercise, defined as the average of the last 30-sec of loaded pedaling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal clinically important difference breathlessness intensity</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>The proportion of participants meeting or exceeding the minimal clinically important difference of ≥1 Borg CR10 scale units in breathlessness intensity at isotime</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal clinically important difference exercise endurance</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>The proportion of participants meeting or exceeding the minimal clinically important difference of ≥101-sec for exercise endurance time at isotime</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety measures - Arterialized carbon dioxide</measure>
    <time_frame>Immediately after each treatment</time_frame>
    <description>Pre to post treatment differences in arterialized carbon dioxide assessed with a blood sample from the warmed earlobe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety measures - Opioid-Related Symptom Distress Scale (ORSDS)</measure>
    <time_frame>Immediately after each treatment</time_frame>
    <description>Pre to post treatment differences in ORSDS-derived measures of opioid-related side-effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety measures - Adverse events</measure>
    <time_frame>Immediately after exercise training program</time_frame>
    <description>The number of participants reporting adverse events (serious and non serious).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Interstitial Lung Disease</condition>
  <arm_group>
    <arm_group_label>Exercise training with morphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) with supervised exercise training.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise training with placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo treatment with supervised exercise training.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exercise training with morphine</intervention_name>
    <description>Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions (three times per week for five weeks) on an electronically braked bike, supervised by a trained exercise specialist. Exercise sessions will be individualized based on participants' peak power output (60% PPO) determined from incremental exercise testing, and progressed to ensure the participant is exercising at a breathlessness intensity rating of between 3-5 Borg CR10 scale units and can complete at least 20-min of continuous cycling. Exercise duration will be increased in 5-min intervals up to 40-min. Thereafter, exercise intensity will be increased by 5-15% of baseline PPO.</description>
    <arm_group_label>Exercise training with morphine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise training with placebo</intervention_name>
    <description>Diluted simple syrup prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions as per the experimental group.</description>
    <arm_group_label>Exercise training with placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females aged 35 years and over&#xD;
&#xD;
          -  Clinical diagnosis of COPD or ILD&#xD;
&#xD;
          -  Cigarette smoking history ≥20 years (COPD only)&#xD;
&#xD;
          -  Post bronchodilator FEV1 &lt;50% predicted and FEV1/FVC &lt;0.70 (COPD only)&#xD;
&#xD;
          -  Chronic breathlessness syndrome (modified Medical Research Council dyspnea score ≥3;&#xD;
             Baseline Dyspnea Index focal score ≤6; and/or an Oxygen Cost Diagram rating ≤50% full&#xD;
             scale despite optimal treatment of the underlying pathophysiology according to&#xD;
             evidence-based clinical practice guidelines&#xD;
&#xD;
          -  Report breathlessness as the main limiting factor to incremental CPET&#xD;
&#xD;
          -  Body mass index &gt;18.5 kg/m2 and &lt;35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Changed respiratory medication dosage and/or frequency of administration in preceding&#xD;
             two weeks&#xD;
&#xD;
          -  Disease exacerbation/hospitalization in preceding six weeks&#xD;
&#xD;
          -  Arterialized capillary CO2 tension (PacCO2) &gt;50 mmHg at rest&#xD;
&#xD;
          -  Self-reported history of drug addiction and/or substance abuse assessed with the&#xD;
             CAIG-aid and SISAP questionnaires&#xD;
&#xD;
          -  Severe excessive daytime sleepiness assessed with the Epworth Sleepiness Scale (score&#xD;
             of 16 out of 24)&#xD;
&#xD;
          -  Currently use anti-seizure and/or opioid drug(s)&#xD;
&#xD;
          -  Use daytime supplemental oxygen&#xD;
&#xD;
          -  Exercise-induced oxyhemoglobin desaturation to &lt;80% on room air&#xD;
&#xD;
          -  Participated in a pulmonary rehabilitation program in preceding 6 months&#xD;
&#xD;
          -  Allergy/sensitivity to opioid drugs&#xD;
&#xD;
          -  Significant extra-pulmonary disease that could impair exercise tolerance&#xD;
&#xD;
          -  Contraindication(s) to cardiopulmonary exercise testing (e.g., significant&#xD;
             cardiovascular, musculoskeletal, neurological disease)&#xD;
&#xD;
          -  Pregnant or currently trying to become pregnant: women of child bearing potential&#xD;
             (defined as having a menstrual period within the last 12 months) will be required to&#xD;
             take a routine (urine) pregnancy test to rule out the possibility of pregnancy&#xD;
&#xD;
          -  Self-report any of the following conditions: anemia or abnormally low blood volume;&#xD;
             asthma; hypothyroidism; Addison's disease; renal insufficiency; hypopituitarism;&#xD;
             severe malnutrition; digestive disease (any form of colitis disease); prostatic&#xD;
             hypertrophy or urethral stricture&#xD;
&#xD;
          -  Use of the blood thinning (anti-coagulant) drug Coumadin, Pradaxa, Xarelto and Eliquis&#xD;
             in previous 2 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dennis Jensen, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dennis Jensen, Ph.D</last_name>
    <phone>514-398-4184</phone>
    <phone_ext>0541</phone_ext>
    <email>denis.jensen@mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hayley Lewthwaite, Ph.D</last_name>
    <phone>514-398-4184</phone>
    <phone_ext>09081</phone_ext>
    <email>hayley.lewthwaite@mail.mcgill.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Montreal Chest Institute of the McGill University Health Center (MUHC)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dennis Jensen, Ph.D.</last_name>
      <phone>514-398-4184</phone>
      <phone_ext>0541</phone_ext>
      <email>dennis.jensen@mcgill.ca</email>
    </contact>
    <contact_backup>
      <last_name>Hayley Lewthwaite, Ph.D</last_name>
      <phone>514-398-4184</phone>
      <phone_ext>09081</phone_ext>
      <email>hayley.lewthwaite@mail.mcgill.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Dennis Jensen, Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hayley Lewthwaite, Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jean Bourbeau, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Benjamin Smith, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Deborah Assayag, MD, MAS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sebastien Gagnon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.mcgill.ca/cerpl/</url>
    <description>Clinical Exercise &amp; Respiratory Physiology Laboratory (CERPL) of McGill University</description>
  </link>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>August 14, 2019</last_update_submitted>
  <last_update_submitted_qc>August 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>McGill University</investigator_affiliation>
    <investigator_full_name>Dennis Jensen, Ph.D.</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Breathlessness</keyword>
  <keyword>Dyspnea</keyword>
  <keyword>Exercise</keyword>
  <keyword>Opioids</keyword>
  <keyword>Morphine</keyword>
  <keyword>Exercise tolerance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</mesh_term>
    <mesh_term>Dyspnea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</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/NCT03824834
org study id: MorEX_2019-5261
nct id: NCT03824834
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to explore the role of low-dose immediate-release oral morphine
      as a novel adjunct pharmacotherapy to enable symptomatic adults with advanced chronic
      obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) to exercise at higher
      intensities for longer durations and maximize the psycho-physiological benefits of a
      supervised exercise training program. We hypothesize that, compared to placebo, exercise
      training with oral morphine will result in relatively greater improvements in exercise
      endurance time and intensity ratings of perceived breathlessness during constant-load
      cardiopulmonary cycle exercise testing (CPET) at 75% of peak power output (PPO).
Supervised exercise training programs (such as pulmonary rehabilitation) are an integral
      component of the clinical management of COPD or ILD; a proven intervention for improving
      symptom burden, quality of life, emotional function, exercise capacity, and risk of
      hospitalization and death. While both low and high intensity exercise training benefits
      adults with COPD or ILD, evidence supports that higher intensity exercise training produces
      relatively greater physiological and symptomatic improvements. High intensity exercise of
      adequate duration is, however, difficult and unpleasant for people with COPD or ILD due to
      heightened exertional symptoms, particularly breathlessness.These symptoms persist despite
      the patient's underlying disease being optimally managed according to evidence-based clinical
      practice guideline standards.

      Low-dose immediate-release oral morphine has recently shown promise as a novel adjunct
      therapy to reduce exertional breathlessness and increase exercise endurance time in people
      with advanced chronic lung disease (COPD). The purpose of this randomized, double-blind,
      placebo-controlled, two-arm pilot study is to further explore the role of low-dose
      immediate-release oral morphine as an adjunct pharmacotherapy to enable symptomatic adults
      with advanced COPD or ILD to exercise at higher intensities for longer durations and maximize
      the psycho-physiological benefits of a 5-week supervised exercise training program.

      Adults with a clinical diagnosis of COPD or ILD and chronic breathlessness syndrome will be
      randomized in a 1:1 ratio to exercise training with oral morphine (ExT+MOR) (n=20; 10 COPD
      and 10 ILD) or exercise training with placebo (diluted simple syrup) (ExT+PLA) (n=20; 10 COPD
      and 10 ILD). All eligible participants will complete four assessment visits (Visits 1, 2, 3
      and 4) and 15 exercise training (T1-15) sessions. Assessment Visits 1 and 3 will include
      post-bronchodilator (400 mg Salbutamol) pulmonary function testing and a symptom-limited
      incremental cardiopulmonary exercise test (CPET) to determine peak power output (PPO). Visits
      2 and 4 will include a symptom-limited constant-load CPET at 75% of the PPO determined at
      Visit 1 and a dual energy x-ray absorptiometry (DEXA) scan to assess body composition.
      Supervised exercise training will be performed three times per week for five weeks on an
      electronically braked cycle ergometer, supervised by a trained exercise specialist. Exercise
      sessions will be individualized based on participants' pre-defined PPO (initial intensity of
      60% PPO), and progressed to ensure the participant is exercising at an intensity
      corresponding to a breathlessness intensity rating of between 3-5 Borg 0-10 category ratio
      scale (CR10) units and can complete at least 20-min of continuous cycling. Exercise duration
      will be increased in 5-min intervals up to 40-min. Thereafter, exercise intensity will be
      increased by 5-15% of baseline PPO.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Study medications, both morphine sulphate and placebo, will be dispensed by the research pharmacist according to the patient's randomization assignment. Neither research staff, nor patients, nor the treating physicians will be aware of the treatment assignment before or after randomization.
measure: Cardiopulmonary exercise testing (CPET) endurance time
time frame: Immediately after exercise training program
description: Cardiopulmonary exercise testing (constant-load) will be used to assess change in endurance time pre to post intervention. Endurance time will be defined as the total duration of loaded pedalling (minutes).
measure: Borg modified 0-10 category ratio scale (Borg CR10) for breathlessness intensity
time frame: Immediately after exercise training program
description: Borg modified 0-10 category ratio scale (Borg CR10) will be used to assess breathlessness intensity during constant-load CPET at isotime, defined as the highest equivalent 2-min interval of exercise completed by a given participant during each of the constant-load CPETs.
measure: Short Form Health Survey (SF-36) for quality of life
time frame: Immediately after exercise training program
description: Short Form Health Survey (SF-36) will be used to assess change in quality of life pre to post intervention.
measure: Multidimensional Dyspnoea Profile for 'usual' breathlessness
time frame: Immediately after exercise training program
description: Multidimensional Dyspnoea Profile will be used to assess change in 'usual' breathlessness pre to post intervention.
measure: Hospital Anxiety and Depression Scale (HADS) for anxiety and depressive symptoms
time frame: Immediately after exercise training program
description: Hospital Anxiety and Depression Scale (HADS) will be used to assess change in anxiety and depressive symptoms pre to post intervention.
measure: DEXA-derived body composition
time frame: Immediately after exercise training program
description: DEXA will be used to assess change in fat free mass pre to post intervention. Fat free mass will be expressed as fat free mass index, which is the fat free mass per kg of total body weight per metre squared of standing height.
measure: CPET physiological response (gas exchange)
time frame: Immediately after exercise training program
description: Breath-by-breath CPET (incremental) parameters will be averaged in 30-sec intervals at rest and during exercise. The change in peak volume of oxygen consumption pre to post will be reported.
CPET parameters will be collected over the first 30-sec period of every second minute during exercise. Three main time points will be used to evaluate exercise test parameters: (1) pre-exercise rest, defined as the steady-state period after at least 3-min of breathing on the mouthpiece while seated at rest before exercise; (2) isotime (as defined above); and (3) peak exercise, defined as the average of the last 30-sec of loaded pedaling.
measure: CPET physiological response (power output)
time frame: Immediately after exercise training program
description: Breath-by-breath CPET (incremental) parameters will be averaged in 30-sec intervals at rest and during exercise. The change in peak power output pre to post will be reported.
CPET parameters will be collected over the first 30-sec period of every second minute during exercise. Three main time points will be used to evaluate exercise test parameters: (1) pre-exercise rest, defined as the steady-state period after at least 3-min of breathing on the mouthpiece while seated at rest before exercise; (2) isotime (as defined above); and (3) peak exercise, defined as the average of the last 30-sec of loaded pedaling.
measure: Minimal clinically important difference breathlessness intensity
time frame: Immediately after exercise training program
description: The proportion of participants meeting or exceeding the minimal clinically important difference of ≥1 Borg CR10 scale units in breathlessness intensity at isotime
measure: Minimal clinically important difference exercise endurance
time frame: Immediately after exercise training program
description: The proportion of participants meeting or exceeding the minimal clinically important difference of ≥101-sec for exercise endurance time at isotime
measure: Safety measures - Arterialized carbon dioxide
time frame: Immediately after each treatment
description: Pre to post treatment differences in arterialized carbon dioxide assessed with a blood sample from the warmed earlobe.
measure: Safety measures - Opioid-Related Symptom Distress Scale (ORSDS)
time frame: Immediately after each treatment
description: Pre to post treatment differences in ORSDS-derived measures of opioid-related side-effects
measure: Safety measures - Adverse events
time frame: Immediately after exercise training program
description: The number of participants reporting adverse events (serious and non serious).
arm group label: Exercise training with morphine
arm group type: Experimental
description: Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) with supervised exercise training.
arm group label: Exercise training with placebo
arm group type: Placebo Comparator
description: Placebo treatment with supervised exercise training.
intervention type: Drug
intervention name: Exercise training with morphine
description: Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions (three times per week for five weeks) on an electronically braked bike, supervised by a trained exercise specialist. Exercise sessions will be individualized based on participants' peak power output (60% PPO) determined from incremental exercise testing, and progressed to ensure the participant is exercising at a breathlessness intensity rating of between 3-5 Borg CR10 scale units and can complete at least 20-min of continuous cycling. Exercise duration will be increased in 5-min intervals up to 40-min. Thereafter, exercise intensity will be increased by 5-15% of baseline PPO.
arm group label: Exercise training with morphine
intervention type: Other
intervention name: Exercise training with placebo
description: Diluted simple syrup prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions as per the experimental group.
arm group label: Exercise training with placebo
criteria: 
gender: All
minimum age: 35 Years
maximum age: N/A
healthy volunteers: No
last name: Dennis Jensen, Ph.D
role: Principal Investigator
affiliation: McGill University
last name: Dennis Jensen, Ph.D
phone: 514-398-4184
phone ext: 0541
email: denis.jensen@mcgill.ca
last name: Hayley Lewthwaite, Ph.D
phone: 514-398-4184
phone ext: 09081
email: hayley.lewthwaite@mail.mcgill.ca
facility: 
status: Recruiting
contact: 
contact backup: 
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country: Canada
url: http://www.mcgill.ca/cerpl/
description: Clinical Exercise & Respiratory Physiology Laboratory (CERPL) of McGill University
responsible party type: Sponsor-Investigator
investigator affiliation: McGill University
investigator full name: Dennis Jensen, Ph.D.
investigator title: Associate Professor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Lung Diseases, Interstitial
mesh term: Dyspnea
mesh term: Morphine
sharing ipd: No