Back to resultsDifferential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Fentanyl Citrate
Combivent
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease
Eligibility Criteria
Inclusion Criteria:
- Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted and FEV1/forced vital capacity (FVC) <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
- Male or female ≥40 yrs of age
- Cigarette smoking history ≥20 pack-years
- Moderate-to-severe chronic activity-related dyspnea as defined by a modified MRC dyspnea scale ≥2, COPD Assessment Test score ≥10 or Baseline Dyspnea Index focal score ≤6 (47-49)
- Ability to perform all study procedures and provide/sign informed consent.
Exclusion Criteria:
- Women of childbearing age who are pregnant or trying to become pregnant
- Diffusing capacity of the lung for carbon monoxide (DLCO) value of <40 %predicted
- Active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation
- History/clinical evidence of asthma, atopy and/or nasal polyps
- History of hypercapnic respiratory failure or a clinical diagnosis of sleep disordered breathing
- History of allergy or adverse response to fentanyl
- Important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
- Use of daytime oxygen or exercise-induced O2 desaturation to < 80% on room air
- Body mass index (BMI) <18.5 or ≥35.0 kg/m2
- Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks
- Use of opioid drugs (e.g., morphine, fentanyl, oxycodone, codeine, etc.) in the previous 4 weeks.
Sites / Locations
- Respiratory Investigation Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Fentanyl Citrate
Combivent Bronchodilator
Arm Description
Single dose, nebulized 100 mcg fentanyl citrate. This is a randomized, double-blind, two-treatment crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate with a constant fraction of 30% inhaled oxygen to that of a nebulized bronchodilator (Combivent). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and combivent at the second treatment visit, patients in the other arm will receive Combivent first and fentanyl second.
Single dose, nebulized Combivent bronchodilator (0.5 mg ipratropium bromide + 2.5 mg salbutamol). This is a randomized, double-blind, two-treatment crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate with a constant fraction of 30% inhaled oxygen to that of a nebulized bronchodilator (Combivent). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and combivent at the second treatment visit, patients in the other arm will receive Combivent first and fentanyl second.
Outcomes
Primary Outcome Measures
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (4-minutes) in both post-treatment constant-load cycle exercise tests.
Secondary Outcome Measures
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test
EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Ventilation at a standardized time during cycle exercise test
Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.
Breathing frequency at a standardized time during cycle exercise test
Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.
Tidal volume at a standardized time during cycle exercise test
Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Inspiratory capacity at a standardized time during cycle exercise test
Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Full Information
NCT ID
NCT03405090
First Posted
January 12, 2018
Last Updated
April 11, 2023
Sponsor
Queen's University
Collaborators
Ontario Lung Association
1. Study Identification
Unique Protocol Identification Number
NCT03405090
Brief Title
Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
Official Title
Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 20, 2017 (Actual)
Primary Completion Date
March 21, 2022 (Actual)
Study Completion Date
March 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Queen's University
Collaborators
Ontario Lung Association
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Activity-related breathlessness (dyspnea) is the dominant symptom and persists despite optimal medical care in as many as 50% of patients with advanced chronic obstructive pulmonary disease (COPD). The objective of this project is to determine the underlying mechanisms of the activity-related breathlessness in patients with advanced COPD. To study the different pathways involved in causing breathlessness, we will compare the effects of two treatments, opiates with oxygen versus bronchodilators, which relieve breathlessness in different ways.
Detailed Description
Dyspnea arises during exercise in COPD patients when there is a mismatch between the ventilatory demand (largely dictated by chemical stimuli) and the capacity to respond to that demand (dictated by mechanical/muscular factors). Our preliminary studies have indicated that treatment with opioids in COPD patients can improve activity related dyspnea by reducing central respiratory neural drive and breathing frequency without a significant change in the respiratory mechanics. By contrast, a reduction in exertional dyspnea following inhaled bronchodilators in COPD was mainly related to an improved respiratory mechanics with increased inspiratory capacity, tidal volume, and inspiratory reserve volume etcetera. By comparing the physiological mechanisms of dyspnea relief during the opiate and bronchodilator therapy, we hope to gain new insights into the mechanisms of dyspnea in COPD by selectively manipulating inspiratory neural drive (nebulized opiates) and abnormal respiratory mechanics (nebulized bronchodilators) within the same individuals. As such, the primary objective of this study is to compare the effects of inhaled opiate with oxygen versus bronchodilator treatments on the intensity of dyspnea, electromyographic estimates of inspiratory neural drive and respiratory mechanics and their interactions during a standardized exercise test using a randomized, controlled, crossover design in patients with COPD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fentanyl Citrate
Arm Type
Active Comparator
Arm Description
Single dose, nebulized 100 mcg fentanyl citrate. This is a randomized, double-blind, two-treatment crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate with a constant fraction of 30% inhaled oxygen to that of a nebulized bronchodilator (Combivent). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and combivent at the second treatment visit, patients in the other arm will receive Combivent first and fentanyl second.
Arm Title
Combivent Bronchodilator
Arm Type
Active Comparator
Arm Description
Single dose, nebulized Combivent bronchodilator (0.5 mg ipratropium bromide + 2.5 mg salbutamol). This is a randomized, double-blind, two-treatment crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate with a constant fraction of 30% inhaled oxygen to that of a nebulized bronchodilator (Combivent). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and combivent at the second treatment visit, patients in the other arm will receive Combivent first and fentanyl second.
Intervention Type
Drug
Intervention Name(s)
Fentanyl Citrate
Other Intervention Name(s)
Inhaled fentanyl
Intervention Description
100 mcg fentanyl citrate will be inhaled via nebulizer
Intervention Type
Drug
Intervention Name(s)
Combivent
Other Intervention Name(s)
Bronchodilator
Intervention Description
0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer
Primary Outcome Measure Information:
Title
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test
Description
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (4-minutes) in both post-treatment constant-load cycle exercise tests.
Time Frame
10-minutes post-treatment
Secondary Outcome Measure Information:
Title
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test
Description
EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Time Frame
10-minutes post-treatment
Title
Ventilation at a standardized time during cycle exercise test
Description
Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.
Time Frame
10-minutes post-treatment
Title
Breathing frequency at a standardized time during cycle exercise test
Description
Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.
Time Frame
10-minutes post-treatment
Title
Tidal volume at a standardized time during cycle exercise test
Description
Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Time Frame
10-minutes post-treatment
Title
Inspiratory capacity at a standardized time during cycle exercise test
Description
Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.
Time Frame
10-minutes post-treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted and FEV1/forced vital capacity (FVC) <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
Male or female ≥40 yrs of age
Cigarette smoking history ≥20 pack-years
Moderate-to-severe chronic activity-related dyspnea as defined by a modified MRC dyspnea scale ≥2, COPD Assessment Test score ≥10 or Baseline Dyspnea Index focal score ≤6 (47-49)
Ability to perform all study procedures and provide/sign informed consent.
Exclusion Criteria:
Women of childbearing age who are pregnant or trying to become pregnant
Diffusing capacity of the lung for carbon monoxide (DLCO) value of <40 %predicted
Active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation
History/clinical evidence of asthma, atopy and/or nasal polyps
History of hypercapnic respiratory failure or a clinical diagnosis of sleep disordered breathing
History of allergy or adverse response to fentanyl
Important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
Use of daytime oxygen or exercise-induced O2 desaturation to < 80% on room air
Body mass index (BMI) <18.5 or ≥35.0 kg/m2
Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks
Use of opioid drugs (e.g., morphine, fentanyl, oxycodone, codeine, etc.) in the previous 4 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denis E O'Donnell, MD, FRCPC
Organizational Affiliation
Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Respiratory Investigation Unit
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
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