Effect of Inhaled Fentanyl on Dyspnea and Exercise Tolerance in Chronic Obstructive Pulmonary Disease (COPD)

Effect of Inhaled Nebulized Fentanyl on Exertional Dyspnea and Exercise Tolerance in Patients With Moderate-to-severe COPD

Breathing discomfort (dyspnea) and activity limitation are dominant symptoms of chronic obstructive pulmonary disease (COPD) and contribute to poor health-related quality of life in this population. Several small, uncontrolled studies and published case reports have provided evidence that inhaled fentanyl, a powerful pain relieving (opioid) medication, may be used to effectively reduce breathing discomfort in patients with advanced disease. However, the mechanisms of this improvement remain unclear. Therefore, the investigators plan to conduct the first randomized, double-blind, placebo-controlled, crossover study designed to explore the possible mechanisms of action of inhaled fentanyl on activity-related dyspnea and exercise performance in patients with advanced COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: normal saline (placebo); Drug: fentanyl

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Respiratory Investigation Unit, Kingston General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Post-bronchodilator forced expiratory volume in 1 sec (FEV1) 30-79% predicted, FEV1/forced vital capacity (FVC) ratio <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;
• A cigarette smoking history ≥20 pack-years;
• Significant chronic activity-related dyspnea as defined by a Baseline Dyspnea Index focal score ≤ 6;
• Body mass index (BMI) between 18.5 and 30.0 kg/m2;
• Able to perform all study procedures and provide/sign informed consent.

Exclusion Criteria:

• A diffusing capacity of the lung for carbon monoxide (DLCO) <40 %predicted;
• Presence of active cardiopulmonary disease other than COPD that could contribute to dyspnea and exercise limitation;
• Clinical diagnosis of sleep disordered breathing;
• A history/clinical evidence of asthma, atopy and/or nasal polyps;
• History of allergy or adverse reaction to fentanyl;
• Presence of important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s);
• Use of daytime oxygen or exercise-induced arterial oxygen desaturation to <80% on room air;
• Use of antidepressant drugs (i.e., monoamine oxidase inhibitors, serotonin reuptake inhibitors) in previous 2 weeks;
• Use of opioid or pain relieving drugs (e.g., morphine, fentanyl, oxycodone, hydromorphone, methadone, levorphanol, codeine, hydrocodone, meperidine) in previous 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; nebulized 0.9% saline placebo	Drug: normal saline (placebo); single dose, 0.9% saline solution
Experimental: fentanyl; nebulized fentanyl citrate (50 mcg)	Drug: fentanyl; single dose, 50 mcg of nebulized fentanyl citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyspnea Intensity Measured by the 10-point Borg Scale During Cycle Exercise	The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and was used to rate the intensity of dyspnea during exercise; therefore, a decrease in this rating signifies an improvement. Dyspnea intensity was assessed at the highest equivalent standardized time achieved in both post-treatment constant work rate cycle exercise tests.	10-minutes post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle Exercise Endurance Time	Constant workrate cycle endurance during tests at 75% of the peak incremental workrate	10-minutes post-treatment

Collaborators and Investigators

• Sponsor: Queen's University
• Investigators: Principal Investigator: Denis E O'Donnell, MD, FRCPC, Queen's University and Kingston General Hospital; Principal Investigator: Deborah Dudgeon, MD, FRCPC, Queen's University and Kingston General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 9, 2009
• First Posted (Estimate): September 10, 2009

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: exercise; COPD; dyspnea; inhaled fentanyl
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: DSS16327