Dyspnea, Healthy
Conditions
Keywords
dyspnea, Laboratory model of dyspnea in healthy subjects
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.
Interventions
DRUGFurosemide
DRUGSaline
Sponsors
National Institute of Nursing Research (NINR)
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject Rating of Breathing Discomfort (Dyspnea) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Dyspnea Profile | Measured before intervention | 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. |
| Urine Output | Cumulative urine output 1 hour after intervention | 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 |
Countries
United States
Participant flow
Pre-assignment details
This was a crossover study of a total of 24 people.
Participants by arm
| Arm | Count |
|---|---|
| F(40) Participants Participants who consented to participate in the study and receive the Aerosol Furosemide (40mg/4ml solution of Saline), Aerosol Saline (4ml), and IV Furosemide (15mg/8ml Saline) Interventions in any sequence. | 12 |
| F(80) Participants Participants who consented to participate in the study and receive the Aerosol Furosemide (80mg/8ml solution of Saline) and two Aerosol Saline (8ml) Interventions in any sequence or receive the Aerosol Furosemide (80mg/8ml solution of Saline), Aerosol Saline (8ml), and IV Furosemide (15mg/8ml Saline) Interventions in any sequence. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | F(80) Participants | F(40) Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Continuous | 23.58 years STANDARD_DEVIATION 4.42 | 31.25 years STANDARD_DEVIATION 12.65 | 27.42 years STANDARD_DEVIATION 10.06 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 9 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerosol Furosemide (40 mg) | Subject Rating of Breathing Discomfort (Dyspnea) | 20 units on a scale | Standard Error 13 |
| Aerosol Saline (4 ml) | Subject Rating of Breathing Discomfort (Dyspnea) | 20 units on a scale | Standard Error 10 |
| IV Furosemide | Subject Rating of Breathing Discomfort (Dyspnea) | 16 units on a scale | Standard Error 13 |
| Aerosol Furosemide (80mg) | Subject Rating of Breathing Discomfort (Dyspnea) | 17 units on a scale | Standard Error 3 |
| Aerosol Saline (8 ml) | Subject Rating of Breathing Discomfort (Dyspnea) | 13 units on a scale | Standard Error 4 |
p-value: 0.99t-test, 2 sided
p-value: 0.32t-test, 2 sided
Secondary
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.
Time frame: Measured before intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Tightness | 3.3 units on a scale | Standard Error 0.8 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | A1 (overall breathing discomfort) | 8.0 units on a scale | Standard Error 0.2 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Muscle Work | 5.5 units on a scale | Standard Error 0.8 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Air hunger | 7.4 units on a scale | Standard Error 0.5 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Mental effort | 6.3 units on a scale | Standard Error 0.7 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Breathing a lot | 4.0 units on a scale | Standard Error 0.9 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Depressed | 0.3 units on a scale | Standard Error 0.2 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Anxious | 3.7 units on a scale | Standard Error 0.7 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Frustrated | 1.6 units on a scale | Standard Error 0.7 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Angry | 0.9 units on a scale | Standard Error 0.5 |
| Aerosol Furosemide (40 mg) | Multidimensional Dyspnea Profile | Afraid | 1.1 units on a scale | Standard Error 0.4 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Anxious | 2.9 units on a scale | Standard Error 0.6 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Tightness | 2.6 units on a scale | Standard Error 0.9 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Mental effort | 3.6 units on a scale | Standard Error 0.9 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Angry | 0.2 units on a scale | Standard Error 0.2 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Breathing a lot | 1.5 units on a scale | Standard Error 0.7 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | A1 (overall breathing discomfort) | 6.4 units on a scale | Standard Error 0.4 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Afraid | 1.2 units on a scale | Standard Error 0.4 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Muscle Work | 2.5 units on a scale | Standard Error 0.7 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Depressed | 0.0 units on a scale | Standard Error 0 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Air hunger | 6.2 units on a scale | Standard Error 0.8 |
| Aerosol Saline (4 ml) | Multidimensional Dyspnea Profile | Frustrated | 1.6 units on a scale | Standard Error 0.6 |
Secondary
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
Time frame: Cumulative urine output 1 hour after intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerosol Furosemide (40 mg) | Urine Output | 1069 ml of urine | Standard Deviation 435 |
| Aerosol Saline (4 ml) | Urine Output | 1320 ml of urine | Standard Deviation 394 |
| IV Furosemide | Urine Output | 500 ml of urine | Standard Deviation 264 |
| Aerosol Furosemide (80mg) | Urine Output | 474 ml of urine | Standard Deviation 146 |
| Aerosol Saline (8 ml) | Urine Output | 1556 ml of urine | Standard Deviation 435 |
p-value: 0.0006t-test, 2 sided
p-value: =0.00001t-test, 2 sided
p-value: 2e-7t-test, 2 sided