Morphine, Dyspnea, Exercise and COPD

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2012 by McGill University
Sponsor:
Information provided by (Responsible Party):
Jean Bourbeau, McGill University
ClinicalTrials.gov Identifier:
NCT01718496
First received: October 15, 2012
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

The investigators are studying the effect of a single dose Opioid drug (Morphine) on dyspnea and exercise tolerance in COPD patients.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Morphine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by McGill University:

Primary Outcome Measures:
  • improvement of dyspnea [ Time Frame: one hour ] [ Designated as safety issue: Yes ]
  • improvement of exercise tolerance [ Time Frame: one hour ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morphine
Patient with advance COPD who will randomly receive single dose oral Morphine
Drug: Morphine
patient with advanced COPD will randomly receive single dose Morphine to assess its effect on dyspnea and exercise tolerance
Other Name: Opioids
Drug: Placebo
patients with advanced COPD on the other study arm will randomly receive Placebo
Other Name: 0.9% Sodium chloride
Placebo Comparator: Placebo
patient with advanced COPD who will receive Placebo
Drug: Morphine
patient with advanced COPD will randomly receive single dose Morphine to assess its effect on dyspnea and exercise tolerance
Other Name: Opioids
Drug: Placebo
patients with advanced COPD on the other study arm will randomly receive Placebo
Other Name: 0.9% Sodium chloride

Detailed Description:

"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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • sever or very sever COPD, i.e. post B2 agonist FEV1<50% predicted
  • age >= 40 years
  • cigarette smoking history > 2 pack yrs
  • ever chronic activity-related dyspnea defined by the combination of A BDI focal score <=6, Modified MRC dyspnea scale >=3 and an OCD rating <=50
  • no change in medication dosage & frequency in the preceding 6 weeks
  • no hospitalization or exacerbation in the preceding 6 weeks

Exclusion Criteria:

  • active cardiopulmonary disease other than COPD
  • contraindication to Cardiopulmonary exercise testing
  • use of daytime oxygen
  • exercise-induced oxyhemoglobin desaturation to <80% on room air
  • Body mass index <18.5 or >30 kg/m2
  • use of antidepressant drugs in the preceding 2 weeks
  • use of opioid drugs in the preceding 4 weeks
  • partial pressure of carbon dioxide PCo2 of >50 mmHg on capillary blood gas
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718496

Contacts
Contact: Dennis Jensen, Ph. D. (514) 398-4184 ext 0572 dennis.jensen@mcgill.ca
Contact: Majed Alghamdi, M.D. 5149341934 ext 32185 majed.rabia@gmail.com

Locations
Canada, Quebec
Montreal Chest Institute Not yet recruiting
Montreal, Quebec, Canada, H2X 2P4
Contact: Dennis Jensen, Ph. D.    (514) 398-4184 ext 0572      
Contact: Majed Alghamdi, M.D.    5149341934 ext 32185      
Sponsors and Collaborators
McGill University
Investigators
Principal Investigator: Dennis Jensen, Ph. D. McGill University
  More Information

No publications provided

Responsible Party: Jean Bourbeau, respirologist, McGill University
ClinicalTrials.gov Identifier: NCT01718496     History of Changes
Other Study ID Numbers: 2844
Study First Received: October 15, 2012
Last Updated: October 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by McGill University:
dyspnea
COPD
exercise tolerance
opioids
morphine
single dose oral Morphine

Additional relevant MeSH terms:
Dyspnea
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014