Chronic Obstructive Pulmonary DiseasePhase 4NCT03405090
Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
A Phase 4 study testing Fentanyl Citrate and Combivent in people with Chronic Obstructive Pulmonary Disease, run by Dr. Denis O'Donnell at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Fentanyl Citrate and Combivent
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 20 Sep 2017to 31 Mar 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Fentanyl Citrate, Combivent
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fentanyl CitrateDrug
Also called Inhaled fentanyl
100 mcg fentanyl citrate will be inhaled via nebulizer
CombiventDrug
Also called Bronchodilator
0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer
| Study group | Role | What they receive |
|---|---|---|
| Fentanyl Citrate | Active comparator | 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. Receives: Drug: Fentanyl Citrate |
| Combivent Bronchodilator | Active comparator | 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. Receives: Drug: Combivent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10-minutes post-treatment
Secondary outcomes (5)
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.
Measured: 10-minutes post-treatment
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.
Measured: 10-minutes post-treatment
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.
Measured: 10-minutes post-treatment
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.
Measured: 10-minutes post-treatment
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.
Measured: 10-minutes post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2018
- Study start20 Sep 2017
- Primary completion21 Mar 2022
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Denis O'Donnell
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Lung Association, Queen's University
- Responsible party
- Sponsor-investigator, Dr. Denis O'Donnell, Queen's University
- Investigators
- Denis E O'Donnell, MD, FRCPC, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03405090
- Sponsor's protocol ID
- DMED-1926-16
- Status last verified
- Apr 2024
- First submitted
- 12 Jan 2018
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
- ClinicalTrials.gov ID
- NCT03405090
- Acronym / sponsor ID
- DMED-1926-16
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Dr. Denis O'DonnellUniversity, hospital or other
- Collaborators
- Ontario Lung Association, Queen's University
- Study start
- 20 Sep 2017 (actual)
- Primary completion
- 21 Mar 2022 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 19 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fentanyl Citrate | Active comparator | Drug: Fentanyl CitrateSingle 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. |
| Combivent Bronchodilator | Active comparator | Drug: CombiventSingle 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. |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fentanyl CitrateAlso: Inhaled fentanyl100 mcg fentanyl citrate will be inhaled via nebulizer | Drug | Fentanyl Citrate |
| CombiventAlso: Bronchodilator0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer | Drug | Combivent Bronchodilator |
Primary outcome
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
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.
5 secondary outcomes
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
Ventilation at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
Breathing frequency at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
Tidal volume at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
Inspiratory capacity at a standardized time during cycle exercise test
Time frame: 10-minutes post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denis E O'Donnell, MD, FRCPC principal investigator
Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fentanyl Citrate and Combivent in people with Chronic Obstructive Pulmonary Disease, run by Dr. Denis O'Donnell at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test (time frame: 10-minutes post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.