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

NCT03405090 | Completed Phase 4

• 1 other identifier: DMED-1926-16
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test

  10-minutes post-treatment

• Ventilation at a standardized time during cycle exercise test

  10-minutes post-treatment

• Breathing frequency at a standardized time during cycle exercise test

  10-minutes post-treatment

• Tidal volume at a standardized time during cycle exercise test

  10-minutes post-treatment

• Inspiratory capacity at a standardized time during cycle exercise test

  10-minutes post-treatment

Study Arms (2)

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.

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.

Drug: Combivent

Interventions

Fentanyl Citrate DRUG

100 mcg fentanyl citrate will be inhaled via nebulizer

Also known as: Inhaled fentanyl

Fentanyl Citrate

Combivent DRUG

0.5 mg ipratropium bromide + 2.5 mg salbutamol will be inhaled via nebulizer

Also known as: Bronchodilator

Combivent Bronchodilator

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dr. Denis O'Donnell: lead
• Ontario Lung Association: collaborator
• Queen's University: collaborator

Study Sites (1)

Respiratory Investigation Unit

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fentanyl; Albuterol, Ipratropium Drug Combination; Bronchodilator Agents

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Ipratropium; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Drug Combinations; Pharmaceutical Preparations; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Asthmatic Agents; Respiratory System Agents; Therapeutic Uses

Study Officials

• Denis E O'Donnell, MD, FRCPC

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: January 19, 2018
• Study Start: September 20, 2017
• Primary Completion: March 21, 2022
• Study Completion: March 31, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)