Aerosol Inhalation Treatment for Dyspnea

Study Overview
=================
Brief Summary
-----------------
The purpose of this protocol is to develop and test optimal delivery of aerosol furosemide, a treatment that has the potential to significantly improve symptom management and enhance the quality of care for patients with intractable dyspnea.

Detailed Description
-----------------
This is study of aerosol treatment in a laboratory model of dyspnea in healthy subjects. This study is the first in a series of studies that will include investigation of a second dose in the laboratory and investigation of the treatment effect in hospitalized patients with refractory dyspnea. The outcome of this first study will determine the details of protocol for the succeeding studies.

Official Title
-----------------
Aerosol Inhalation Treatment for Dyspnea

Conditions
-----------------
Healthy, Dyspnea

Intervention / Treatment
-----------------
* Drug: Furosemide
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Exclusion Criteria: Unstable heart or circulation disease Stroke Seizure disorder Severe migraine headaches Liver or kidney disease Adrenal gland problem (Pheochromocytoma) Nerve problems that may affect your breathing sensation Brain cancer Drug or alcohol problem Systemic lupus erythematosis (SLE) High levels of depression, panic disorder, or other significant mental health problems Serious ongoing pain Pregnant Under 18 years old Not Fluent in English

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F(40), then Saline, then IV.F<br>On Test Day 1, participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 4ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |
| Experimental: IV.F, then F(40), then Saline<br>On Test Day 1, participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 4ml by inhalation for 5-10 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |
| Experimental: Saline, then F(40), then IV.F<br>On Test Day 1, participants received Aerosol Saline 4ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 3), participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |
| Experimental: F(80), then Saline, then Saline<br>On Test Day 1, participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |
| Experimental: Saline, then F(80), then Saline<br>On Test Day 1, participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |
| Experimental: Saline, then Saline, then F(80)<br>On Test Day 1, participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Rating of Breathing Discomfort (Dyspnea) | Change in breathing discomfort (dyspnea) rating at benchmark PETCO2 using a visual analog scale. The change in breathing discomfort is expressed as units on a 0% to 100% continuous scale, where higher values represent more dyspnea. The change is represented as the rating of breathing discomfort after the intervention minus the rating of breathing discomfort before the intervention. | The breathing discomfort ratings were taken as an average of all ratings during runs before intervention and the first two runs after intervention. The 1st and 2nd post-runs began (on average) 12 minutes and 49 minute after intervention, respectively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multidimensional Dyspnea Profile | Characterization of subject's response to laboratory dyspnea model. Data are from a baseline pre-treatment test on the first drug or placebo treatment day for the subjects used in the main analysis. Subjects were asked to complete the MDP with reference to the last 30 sec of each run. To weigh subjects equally, we selected one run from each subject: the first run that terminated in a rating of overall breathing discomfort (A1) of 50 to 90% of full scale. The units of measurement are expressed as units on a 0 to 10 scale measuring intensity of a given quality, with higher values indicating greater intensity and 10 representing maximum perceived intensity. | Measured before intervention | 
| Urine Output | Diuresis is an expected effect of furosemide. To the extent that aerosol furosemide is absorbed into the blood, diuresis is an expected 'side effect' of this treatment | Cumulative urine output 1 hour after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dyspnea, Laboratory model of dyspnea in healthy subjects