Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03405090
• Other study ID #: DMED-1926-16
• Status: Completed
• Phase: Phase 4
• Start date: September 20, 2017
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2024
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 31, 2023
• Est. primary completion date: March 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted and FEV1/forced vital capacity (FVC) <70%

2. 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

3. Male or female =40 yrs of age

4. Cigarette smoking history =20 pack-years

5. 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)

6. Ability to perform all study procedures and provide/sign informed consent.

Exclusion Criteria:

1. Women of childbearing age who are pregnant or trying to become pregnant

2. Diffusing capacity of the lung for carbon monoxide (DLCO) value of <40 %predicted

3. Active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation

4. History/clinical evidence of asthma, atopy and/or nasal polyps

5. History of hypercapnic respiratory failure or a clinical diagnosis of sleep disordered breathing

6. History of allergy or adverse response to fentanyl

7. Important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)

8. Use of daytime oxygen or exercise-induced O2 desaturation to < 80% on room air

9. Body mass index (BMI) <18.5 or =35.0 kg/m2

10. Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks

11. Use of opioid drugs (e.g., morphine, fentanyl, oxycodone, codeine, etc.) in the previous 4 weeks.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Dyspnea
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Fentanyl Citrate
100 mcg fentanyl citrate will be inhaled via nebulizer
• Combivent
0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer

Locations

Country	Name	City	State
Canada	Respiratory Investigation Unit	Kingston	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Dr. Denis O'Donnell	Ontario Lung Association, Queen's University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	10-minutes post-treatment
Secondary	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.	10-minutes post-treatment
Secondary	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.	10-minutes post-treatment
Secondary	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.	10-minutes post-treatment
Secondary	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.	10-minutes post-treatment
Secondary	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.	10-minutes post-treatment