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

• Sponsor: Queen's University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00974220
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: fentanyl; Drug: normal saline (placebo)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Inhaled Nebulized Fentanyl on Exertional Dyspnea and Exercise Tolerance in Patients With Moderate-to-severe COPD
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo nebulized 0.9% saline placebo	Drug: normal saline (placebo); single dose, 0.9% saline solution
Experimental: fentanyl nebulized fentanyl citrate (50 mcg)	Drug: fentanyl; single dose, 50 mcg of nebulized fentanyl citrate

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Cycle Exercise Endurance Time [10-minutes post-treatment]

   Constant workrate cycle endurance during tests at 75% of the peak incremental workrate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Respiratory Investigation Unit, Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7

Sponsors and Collaborators

• Queen's University

Investigators

• Principal Investigator: Denis E O'Donnell, MD, FRCPC, Queen's University and Kingston General Hospital
• Principal Investigator: Deborah Dudgeon, MD, FRCPC, Queen's University and Kingston General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Denis O'Donnell, Principal Investigator, Queen's University
• ClinicalTrials.gov Identifier: NCT00974220
• Other Study ID Numbers: DSS16327
• First Posted: Sep 10, 2009
• Last Update Posted: Jul 12, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Dr. Denis O'Donnell, Principal Investigator, Queen's University: inhaled fentanyl; dyspnea; exercise; COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea; Fentanyl

Study Results

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 Detail	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.

Arm/Group Title	Placebo - Fentanyl (Order)	Fentanyl - Placebo (Order)
Arm/Group Description	nebulized 0.9% saline placebo in period 1, nebulized fentanyl citrate 50mcg in period 2	nebulized fentanyl citrate (50 mcg) in period 1, nebulized 0.9% saline placebo in period 2
Period Title: Treatment Period 1
STARTED	9	7
COMPLETED	7	5
NOT COMPLETED	2	2
Period Title: Treatment Period 1
STARTED	7	5
COMPLETED	7	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo - Fentanyl (Order)	Fentanyl - Placebo (Order)	Total
Arm/Group Description	nebulized saline placebo in period 1, nebulized fentanyl citrate in period 2.	nebulized fentanyl citrate in period 1, nebulized saline placebo in period 2.	Total of all reporting groups
Overall Participants	9	7	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (8)	66 (10)	68 (9)
Sex: Female, Male (Count of Participants)
Female	3 33.3%	4 57.1%	7 43.8%
Male	6 66.7%	3 42.9%	9 56.3%
Region of Enrollment (participants) [Number]
Canada	9 100%	7 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise
Description	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

Outcome Measure Data

Analysis Population Description

Subjects who completed both treatment arms of the crossover study were included in the primary analysis.

Arm/Group Title	Placebo	Fentanyl
Arm/Group Description	nebulized 0.9% saline placebo	nebulized fentanyl citrate (50 mcg)
Measure Participants	12	12
Mean (Standard Error) [units on a scale]	2.6 (0.5)	2.0 (0.5)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Subjects completing both treatment arms were included in this analysis

Arm/Group Title	Placebo	Fentanyl
Arm/Group Description	nebulized 0.9% saline placebo	nebulized fentanyl citrate (50 mcg)
Measure Participants	12	12
Mean (Standard Error) [minutes]	6.04 (0.56)	7.34 (0.70)

Adverse Events

Time Frame	During visit, with appropriate follow-up to resolution of adverse event
Arm/Group Title	Placebo		Fentanyl
Arm/Group Description	nebulized 0.9% saline placebo		nebulized fentanyl citrate (50 mcg)
All Cause Mortality
	Placebo		Fentanyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Fentanyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Fentanyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		1/16 (6.3%)
Nervous system disorders
lightheadedness, dizziness and mild nausea	1/16 (6.3%)	1	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
severe dyspnea	1/16 (6.3%)	1	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.