Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea

Interstitial Lung Disease Clinical Trial

Official title:

Use of Nebulized Fentanyl in Patients With Mild-to-Moderate Interstitial Lung Disease and Chronic Dyspnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018756
• Other study ID #: DMED-1921-16
• Status: Completed
• Phase: Phase 3
• Start date: January 2017
• Est. completion date: November 30, 2020

Study information

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

Clinical Trial Summary

Patients with interstitial lung disease (ILD) experience distressing activity-related respiratory discomfort which is challenging to manage therapeutically. Interventions such as pulmonary rehabilitation, collaborative self-management, supplemental oxygen therapy and oral opiate medications, are variably effective and therapeutic responses to each in individual patients are difficult to predict. The purpose of this study is to evaluate the acute effects of inhaled opiate therapy (fentanyl citrate) on breathing discomfort (dyspnea) in individuals with mild-to-moderate ILD, as well as examine the potential mechanisms of dyspnea relief.

Description:

Treatment with opioids can improve activity related dyspnea by reducing central respiratory neural drive. Inhaled fentanyl citrate is an opioid that is generally well tolerated and has been shown to effectively relieve respiratory discomfort without causing systemic side-effects, although its mechanism of action are poorly understood. Based on the current evidence, non-sedating, rapidly active inhaled fentanyl represents a possible alternative and effective treatment of severe dyspnea in patients with ILD who require urgent treatment. As such, the primary objective of this study is to examine the acute effects of nebulized fentanyl on dyspnea intensity and quality in patients with mild-to-moderate ILD, as well as examine the neurophysiological mechanisms of dyspnea relief during fentanyl inhalation. It is believed that fentanyl when compared with placebo, will reduce inspiratory neural drive to the diaphragm and breathing frequency, resulting in improvements in dyspnea intensity during physical exertion. Alternatively, dyspnea relief after inhaled fentanyl may be independent of changes in neural drive, and instead linked to the presence of opioid receptors in the lungs that modulate afferent inputs to the brain, thereby favourably influencing perceived dyspnea.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 30, 2020
• Est. primary completion date: June 25, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Fibrotic interstitial lung disease (ILD) diagnosis confirmed by specialty ILD clinic

• A total lung capacity (TLC) <lower limit of normal and =60%predicted, a forced vital capacity (FVC) <lower limit of normal and =60%predicted, and a forced expiratory volume in 1 second (FEV1)/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.

• Moderate-to-severe chronic activity related dyspnea as defined by a Baseline Dyspnea Index total score =9, modified Medical Research Council score >1, or oxygen cost diagram.

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

Exclusion Criteria:

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

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

• Presence of active cardiopulmonary disease other than ILD that could contribute to dyspnea and exercise limitation.

• History of allergy or adverse reaction to fentanyl.

• History of allergy or adverse reaction to latex

• Presence of contraindications to pulmonary function or clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s).

• Use of ambulatory oxygen or exercise-induced oxygen 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 the previous 2 weeks.

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

Note: Healthy volunteers will only be used to assist in the characterization of the IPF study group, i.e., for comparison of baseline exercise responses. They will not undergo treatment.

Related Conditions & MeSH terms

• Dyspnea
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial

Intervention

Drug:
• Fentanyl Citrate
100 mcg fentanyl citrate will be inhaled via nebulizer.
• Placebo
0.9% saline solution will be inhaled via nebulizer

Locations

Country	Name	City	State
Canada	Respiratory Investigation Unit, Queen's University	Kingston	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Dr. Denis O'Donnell	Boehringer Ingelheim

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 ergometer exercise	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 ergometer tests.	10-minutes post-treatment
Secondary	Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise	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	Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.	10-minutes post-treatment
Secondary	Breathing frequency at a standardized time during cycle exercise	Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.	10-minutes post-treatment
Secondary	Tidal volume at a standardized time during cycle exercise	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	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