Effect of Inhaled Fentanyl on Dyspnea and Exercise Tolerance in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Breathing discomfort (dyspnea) and activity limitation are dominant symptoms of chronic obstructive pulmonary disease (COPD) and contribute to poor health-related quality of life in this population. Several small, uncontrolled studies and published case reports have provided evidence that inhaled fentanyl, a powerful pain relieving (opioid) medication, may be used to effectively reduce breathing discomfort in patients with advanced disease. However, the mechanisms of this improvement remain unclear. Therefore, the investigators plan to conduct the first randomized, double-blind, placebo-controlled, crossover study designed to explore the possible mechanisms of action of inhaled fentanyl on activity-related dyspnea and exercise performance in patients with advanced COPD.

Official Title
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Effect of Inhaled Nebulized Fentanyl on Exertional Dyspnea and Exercise Tolerance in Patients With Moderate-to-severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: fentanyl
* Drug: normal saline (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted, FEV1/forced vital capacity (FVC) ratio <70%; Clinically stable as defined by no changes in medication dosage or frequency of administration with no exacerbations or hospital admissions in the preceding 6 weeks; A cigarette smoking history ≥20 pack-years; Significant chronic activity-related dyspnea as defined by a Baseline Dyspnea Index focal score ≤ 6; Body mass index (BMI) between 18.5 and 30.0 kg/m2; Able to perform all study procedures and provide/sign informed consent. Exclusion Criteria: A diffusing capacity of the lung for carbon monoxide (DLCO) <40 %predicted; Presence of active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation; Clinical diagnosis of sleep disordered breathing; A history/clinical evidence of asthma, atopy and/or nasal polyps; History of allergy or adverse reaction to fentanyl; Presence of important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s); Use of daytime oxygen or exercise-induced arterial oxygen desaturation to <80% on room air; Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks; Use of opioid or pain relieving drugs (e.g., morphine, fentanyl, oxycodone, hydromorphone, methadone, levorphanol, codeine, hydrocodone, meperidine) in previous 4 weeks.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>nebulized 0.9% saline placebo | Drug: normal saline (placebo)<br>* single dose, 0.9% saline solution<br>|
| Experimental: fentanyl<br>nebulized fentanyl citrate (50 mcg) | Drug: fentanyl<br>* single dose, 50 mcg of nebulized fentanyl citrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise | The 10-point Borg scale ranges from 0 nothing at all to 10 maximal/extremely strong and was used to rate the intensity of dyspnea during exercise; therefore, a decrease in this rating signifies an improvement. Dyspnea intensity was assessed at the highest equivalent standardized time achieved in both post-treatment constant work rate cycle exercise tests. | 10-minutes post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cycle Exercise Endurance Time | Constant workrate cycle endurance during tests at 75% of the peak incremental workrate | 10-minutes post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inhaled fentanyl, dyspnea, exercise, COPD