<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/NCT01718496</url>
  </required_header>
  <id_info>
    <org_study_id>2844</org_study_id>
    <nct_id>NCT01718496</nct_id>
  </id_info>
  <brief_title>Morphine, Dyspnea, Exercise and COPD</brief_title>
  <official_title>Physiological Mechanisms of Dyspnea Relief and Improved Exercise Tolerance After Treatment With Oral Morphine in Patients With Advanced Chronic Obstructive Pulmonary Disease (COPD).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are studying the effect of a single dose Opioid drug (Morphine) on dyspnea&#xD;
      and exercise tolerance in COPD patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      &quot;Dyspnea&quot; refers to the subjective awareness of breathing discomfort that typically&#xD;
      accompanies an increase in physical activity, particularly in patients with Chronic&#xD;
      Obstructive Pulmonary Disease (COPD). In these patients, the symptom of dyspnea contributes&#xD;
      significantly to exercise intolerance and an impoverished health-related quality of life.&#xD;
      Alleviating dyspnea and improving functional capacity are, therefore, among the principal&#xD;
      goals of COPD management, i.e., response to therapy. Nevertheless, the effective management&#xD;
      of dyspnea and exercise intolerance remains an elusive goal for healthcare providers and&#xD;
      current strategies aimed at reversing the patients' underlying chronic disease (e.g.,&#xD;
      bronchodilators, corticosteroids, supplemental oxygen) are only partially successful in this&#xD;
      regard. Evidence-based clinical practice guidelines recommend that, under these&#xD;
      circumstances, pain-relieving (opioid) medications may be used for the pharmacologic&#xD;
      management of refractory dyspnea and activity-limitation in COPD. Indeed, a handful of&#xD;
      published studies provide evidence to suggest that single-dose treatment with morphine or&#xD;
      dihydrocodeine improves dyspnea and exercise performance by ~20% in patients with COPD.&#xD;
      Nevertheless, little information is available on the physiological mechanisms by which opioid&#xD;
      drugs contribute to these improvements in such patients. From a clinical management&#xD;
      perspective, this information becomes crucial if we are to optimize the management of&#xD;
      exertional symptoms in patients with advanced COPD who remain incapacitated by dyspnea,&#xD;
      despite receiving optimal care from their healthcare provider for their underlying disease.&#xD;
      Therefore, the purpose of the proposed randomized, double-blind, placebo-controlled,&#xD;
      cross-over study is (1) to test the hypothesis that single-dose administration of oral&#xD;
      morphine sulphate will improve exertional dyspnea and exercise tolerance in patients with&#xD;
      advanced COPD and (2) elucidate the physiological underpinnings of these improvements. To&#xD;
      this end, we will compare the effects of single-dose administration of oral morphine sulphate&#xD;
      (0.1 mg/kg, equivalent to 7.5 mg for an average 75 kg man) and placebo on dyspnea (sensory&#xD;
      intensity and affective responses) and exercise endurance time during symptom-limited&#xD;
      constant-work-rate cardiopulmonary cycle exercise testing in symptomatic patients with&#xD;
      severe-to-very severe COPD. To explore possible physiological mechanisms of symptom relief,&#xD;
      we will measure spirometry parameters, plethysmographic lung volumes and plasma morphine&#xD;
      concentrations; perform detailed assessments of central neural respiratory motor drive (i.e.,&#xD;
      diaphragm electromyography), contractile respiratory muscle function (i.e., esophageal,&#xD;
      gastric and transdiaphragmatic pressures), operating lung volumes, ventilation, breathing&#xD;
      pattern, pulmonary gas exchange and cardio-metabolic function during exercise; and employ a&#xD;
      novel multi-dimensional evaluation technique that permits simultaneous measurement of the&#xD;
      sensory intensity and affective dimensions of dyspnea.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">August 2016</completion_date>
  <primary_completion_date type="Anticipated">August 2016</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, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>improvement of dyspnea</measure>
    <time_frame>one hour</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>improvement of exercise tolerance</measure>
    <time_frame>one hour</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient with advance COPD who will randomly receive single dose oral Morphine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>patient with advanced COPD who will receive Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>patient with advanced COPD will randomly receive single dose Morphine to assess its effect on dyspnea and exercise tolerance</description>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Opioids</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>patients with advanced COPD on the other study arm will randomly receive Placebo</description>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>0.9% Sodium chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  sever or very sever COPD, i.e. post B2 agonist FEV1&lt;50% predicted&#xD;
&#xD;
          -  age &gt;= 40 years&#xD;
&#xD;
          -  cigarette smoking history &gt; 2 pack yrs&#xD;
&#xD;
          -  ever chronic activity-related dyspnea defined by the combination of A BDI focal score&#xD;
             &lt;=6, Modified MRC dyspnea scale &gt;=3 and an OCD rating &lt;=50&#xD;
&#xD;
          -  no change in medication dosage &amp; frequency in the preceding 6 weeks&#xD;
&#xD;
          -  no hospitalization or exacerbation in the preceding 6 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active cardiopulmonary disease other than COPD&#xD;
&#xD;
          -  contraindication to Cardiopulmonary exercise testing&#xD;
&#xD;
          -  use of daytime oxygen&#xD;
&#xD;
          -  exercise-induced oxyhemoglobin desaturation to &lt;80% on room air&#xD;
&#xD;
          -  Body mass index &lt;18.5 or &gt;30 kg/m2&#xD;
&#xD;
          -  use of antidepressant drugs in the preceding 2 weeks&#xD;
&#xD;
          -  use of opioid drugs in the preceding 4 weeks&#xD;
&#xD;
          -  partial pressure of carbon dioxide PCo2 of &gt;50 mmHg on capillary blood gas&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</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>0572</phone_ext>
    <email>dennis.jensen@mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Majed Alghamdi, M.D.</last_name>
    <phone>5149341934</phone>
    <phone_ext>32185</phone_ext>
    <email>majed.rabia@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Montreal Chest Institute</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 2P4</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>0572</phone_ext>
    </contact>
    <contact_backup>
      <last_name>Majed Alghamdi, M.D.</last_name>
      <phone>5149341934</phone>
      <phone_ext>32185</phone_ext>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>September 22, 2015</last_update_submitted>
  <last_update_submitted_qc>September 22, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University</investigator_affiliation>
    <investigator_full_name>Jean Bourbeau</investigator_full_name>
    <investigator_title>respirologist</investigator_title>
  </responsible_party>
  <keyword>dyspnea</keyword>
  <keyword>COPD</keyword>
  <keyword>exercise tolerance</keyword>
  <keyword>opioids</keyword>
  <keyword>morphine</keyword>
  <keyword>single dose oral Morphine</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>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>
  <!-- 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/NCT01718496
org study id: 2844
nct id: NCT01718496
lead sponsor: 
has dmc: Yes
The investigators are studying the effect of a single dose Opioid drug (Morphine) on dyspnea
      and exercise tolerance in COPD patients.
"Dyspnea" refers to the subjective awareness of breathing discomfort that typically
      accompanies an increase in physical activity, particularly in patients with Chronic
      Obstructive Pulmonary Disease (COPD). In these patients, the symptom of dyspnea contributes
      significantly to exercise intolerance and an impoverished health-related quality of life.
      Alleviating dyspnea and improving functional capacity are, therefore, among the principal
      goals of COPD management, i.e., response to therapy. Nevertheless, the effective management
      of dyspnea and exercise intolerance remains an elusive goal for healthcare providers and
      current strategies aimed at reversing the patients' underlying chronic disease (e.g.,
      bronchodilators, corticosteroids, supplemental oxygen) are only partially successful in this
      regard. Evidence-based clinical practice guidelines recommend that, under these
      circumstances, pain-relieving (opioid) medications may be used for the pharmacologic
      management of refractory dyspnea and activity-limitation in COPD. Indeed, a handful of
      published studies provide evidence to suggest that single-dose treatment with morphine or
      dihydrocodeine improves dyspnea and exercise performance by ~20% in patients with COPD.
      Nevertheless, little information is available on the physiological mechanisms by which opioid
      drugs contribute to these improvements in such patients. From a clinical management
      perspective, this information becomes crucial if we are to optimize the management of
      exertional symptoms in patients with advanced COPD who remain incapacitated by dyspnea,
      despite receiving optimal care from their healthcare provider for their underlying disease.
      Therefore, the purpose of the proposed randomized, double-blind, placebo-controlled,
      cross-over study is (1) to test the hypothesis that single-dose administration of oral
      morphine sulphate will improve exertional dyspnea and exercise tolerance in patients with
      advanced COPD and (2) elucidate the physiological underpinnings of these improvements. To
      this end, we will compare the effects of single-dose administration of oral morphine sulphate
      (0.1 mg/kg, equivalent to 7.5 mg for an average 75 kg man) and placebo on dyspnea (sensory
      intensity and affective responses) and exercise endurance time during symptom-limited
      constant-work-rate cardiopulmonary cycle exercise testing in symptomatic patients with
      severe-to-very severe COPD. To explore possible physiological mechanisms of symptom relief,
      we will measure spirometry parameters, plethysmographic lung volumes and plasma morphine
      concentrations; perform detailed assessments of central neural respiratory motor drive (i.e.,
      diaphragm electromyography), contractile respiratory muscle function (i.e., esophageal,
      gastric and transdiaphragmatic pressures), operating lung volumes, ventilation, breathing
      pattern, pulmonary gas exchange and cardio-metabolic function during exercise; and employ a
      novel multi-dimensional evaluation technique that permits simultaneous measurement of the
      sensory intensity and affective dimensions of dyspnea.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: improvement of dyspnea
time frame: one hour
measure: improvement of exercise tolerance
time frame: one hour
arm group label: Morphine
arm group type: Active Comparator
description: Patient with advance COPD who will randomly receive single dose oral Morphine
arm group label: Placebo
arm group type: Placebo Comparator
description: patient with advanced COPD who will receive Placebo
intervention type: Drug
intervention name: Morphine
description: patient with advanced COPD will randomly receive single dose Morphine to assess its effect on dyspnea and exercise tolerance
arm group label: Morphine
arm group label: Placebo
other name: Opioids
intervention type: Drug
intervention name: Placebo
description: patients with advanced COPD on the other study arm will randomly receive Placebo
arm group label: Morphine
arm group label: Placebo
other name: 0.9% Sodium chloride
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
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: 0572
email: dennis.jensen@mcgill.ca
last name: Majed Alghamdi, M.D.
phone: 5149341934
phone ext: 32185
email: majed.rabia@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: McGill University
investigator full name: Jean Bourbeau
investigator title: respirologist
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Dyspnea
mesh term: Morphine