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

Primary Purpose

Interstitial Lung Disease

Status

Completed

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

Fentanyl Citrate

Placebo

About this trial

This is an interventional treatment trial for Interstitial Lung Disease

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Respiratory Investigation Unit, Queen's University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Fentanyl Citrate

Placebo

Arm Description

Single dose, nebulized 100 mcg fentanyl citrate. This is a double-blind, placebo-controlled, two-period crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate to that of a placebo (0.9% saline). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and placebo at the second treatment visit, patients in the other arm will receive placebo first and fentanyl second.

Single dose, nebulized 0.9% saline solution. This is a double-blind, placebo-controlled, two-period crossover study comparing the effects of a single dose of nebulized 100 mcg fentanyl citrate to that of a placebo (0.9% saline). Treatments will be in randomized order: patients in one study arm will receive fentanyl at the first treatment visit and placebo at the second treatment visit, patients in the other arm will receive placebo first and fentanyl second.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT03018756

First Posted

December 20, 2016

Last Updated

April 21, 2022

Sponsor

Queen's University

Collaborators

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT03018756

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

January 2017 (Actual)

Primary Completion Date

June 25, 2018 (Actual)

Study Completion Date

November 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Queen's University

Collaborators

Boehringer Ingelheim

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Interstitial Lung Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fentanyl Citrate

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fentanyl Citrate

Other Intervention Name(s)

inhaled fentanyl

Intervention Description

100 mcg fentanyl citrate will be inhaled via nebulizer.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

normal saline

Intervention Description

0.9% saline solution will be inhaled via nebulizer

Primary Outcome Measure Information:

Title

Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle ergometer exercise

Description

Time Frame

10-minutes post-treatment

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

10-minutes post-treatment

Title

Ventilation at a standardized time during cycle exercise

Description

Exercise measurements of minute ventilation will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.

Time Frame

10-minutes post-treatment

Title

Breathing frequency at a standardized time during cycle exercise

Description

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.

Time Frame

10-minutes post-treatment

Title

Tidal volume at a standardized time during cycle exercise

Description

Exercise measurements of tidal volume will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.

Time Frame

10-minutes post-treatment

Title

Inspiratory capacity at a standardized time during cycle exercise

Description

Exercise measurements of inspiratory capacity will be compared at a standardized time (4-minutes) during both post-treatment constant-load cycle exercise tests.

Time Frame

10-minutes post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Denis E O'Donnell, MD, FRCPC

Organizational Affiliation

Queen's University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Respiratory Investigation Unit, Queen's University

City

Kingston

State/Province

Ontario

ZIP/Postal Code

K7L 2V7

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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