Chronic Obstructive Pulmonary Disease
Conditions
Keywords
inhaled fentanyl, dyspnea, exercise, COPD
Brief summary
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.
Interventions
DRUGfentanyl
single dose, 50 mcg of nebulized fentanyl citrate
DRUGnormal saline (placebo)
single dose, 0.9% saline solution
Sponsors
Queen's University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise | 10-minutes post-treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cycle Exercise Endurance Time | 10-minutes post-treatment | Constant workrate cycle endurance during tests at 75% of the peak incremental workrate |
Countries
Canada
Participant flow
Recruitment details
Recruitment took place between February and October 2010. Subjects were recruited from respiratory outpatient clinics and from a database of subjects who had previously taken part in research studies in COPD.
Pre-assignment details
No enrolled subjects were excluded prior to group assignment. 7 subjects were assigned a treatment order of fentanyl-placebo (2 were withdrawn after period 1) and 9 subjects were assigned a treatment order of placebo-fentanyl (2 were withdrawn after period 1). Therefore, there was complete data from 12 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Fentanyl (Order) nebulized saline placebo in period 1, nebulized fentanyl citrate in period 2. | 9 |
| Fentanyl - Placebo (Order) nebulized fentanyl citrate in period 1, nebulized saline placebo in period 2. | 7 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 2 | 1 |
| Treatment Period 1 | noncompliant subjects | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo - Fentanyl (Order) | Fentanyl - Placebo (Order) | Total |
|---|---|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 8 | 66 years STANDARD_DEVIATION 10 | 68 years STANDARD_DEVIATION 9 |
| Region of Enrollment Canada | 9 participants | 7 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
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.
Time frame: 10-minutes post-treatment
Population: Subjects who completed both treatment arms of the crossover study were included in the primary analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise | 2.6 units on a scale | Standard Error 0.5 |
| Fentanyl | Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise | 2.0 units on a scale | Standard Error 0.5 |
Secondary
Cycle Exercise Endurance Time
Constant workrate cycle endurance during tests at 75% of the peak incremental workrate
Time frame: 10-minutes post-treatment
Population: Subjects completing both treatment arms were included in this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cycle Exercise Endurance Time | 6.04 minutes | Standard Error 0.56 |
| Fentanyl | Cycle Exercise Endurance Time | 7.34 minutes | Standard Error 0.7 |