Morphine, Dyspnea, Exercise and COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01718496
• Other study ID #: 2844
• Status: Recruiting
• Phase: Phase 3
• First received: October 15, 2012
• Last updated: September 22, 2015
• Start date: July 2014
• Est. completion date: August 2016

Study information

• Verified date: September 2015
• Source: McGill University Health Center
• Contact: Dennis Jensen, Ph. D.
• Phone: (514) 398-4184
• Email: dennis.jensen[@]mcgill.ca
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Morphine
patient with advanced COPD will randomly receive single dose Morphine to assess its effect on dyspnea and exercise tolerance
• Placebo
patients with advanced COPD on the other study arm will randomly receive Placebo

Locations

Country	Name	City	State
Canada	Montreal Chest Institute	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Center

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	improvement of dyspnea		one hour	Yes
Primary	improvement of exercise tolerance		one hour	Yes