Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03405090
Recruitment Status : Suspended (Temporarily suspended due to COVID-19)
First Posted : January 19, 2018
Last Update Posted : September 17, 2020
Sponsor:
Collaborator:
Ontario Lung Association
Information provided by (Responsible Party):
Dr. Denis O'Donnell, Queen's University

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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Fentanyl Citrate Drug: Combivent Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Differential Mechanisms of Dyspnea Relief in Advanced COPD: Opiates vs. Bronchodilators
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Fentanyl Citrate
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.
Drug: Fentanyl Citrate
100 mcg fentanyl citrate will be inhaled via nebulizer
Other Name: Inhaled fentanyl

Active Comparator: Combivent Bronchodilator
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.
Drug: Combivent
0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer
Other Name: Bronchodilator




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test [ Time Frame: 10-minutes post-treatment ]
    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.

  2. Ventilation at a standardized time during cycle exercise test [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.

  3. Breathing frequency at a standardized time during cycle exercise test [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load exercise tests.

  4. Tidal volume at a standardized time during cycle exercise test [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.

  5. Inspiratory capacity at a standardized time during cycle exercise test [ Time Frame: 10-minutes post-treatment ]
    Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03405090


Locations
Layout table for location information
Canada, Ontario
Respiratory Investigation Unit
Kingston, Ontario, Canada, K7L 2V7
Sponsors and Collaborators
Queen's University
Ontario Lung Association
Investigators
Layout table for investigator information
Principal Investigator: Denis E O'Donnell, MD, FRCPC Queen's University
  Study Documents (Full-Text)

Documents provided by Dr. Denis O'Donnell, Queen's University:
Layout table for additonal information
Responsible Party: Dr. Denis O'Donnell, Principal Investigator, Queen's University
ClinicalTrials.gov Identifier: NCT03405090    
Other Study ID Numbers: DMED-1926-16
First Posted: January 19, 2018    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Dyspnea
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Fentanyl
Bronchodilator Agents
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Autonomic Agents
Anti-Asthmatic Agents
Respiratory System Agents