Healthy Subjects
Conditions
Brief summary
The purpose of this research study is to learn about how long hypertonic saline (HS) works in healthy subjects. Inhaled hypertonic saline is one of the medications used to treat Cystic Fibrosis (CF). In CF and more common lung diseases like chronic bronchitis, mucus builds up in the lungs. Hypertonic saline and other medications currently being developed may help patients with these lung diseases by speeding up mucus clearance from the lung. For these treatments to be effective, they likely need to be able to act for at lease several hours. Investigators are able to measure how lung treatments like hypertonic saline work by conducting a Mucociliary Clearance (MCC) scan. Currently, the investigators do not know how long hypertonic saline works in people who do not have CF. Investigators plan to use this information to improve the design and testing of new treatments for patients with chronic bronchitis. Objectives: 1. The investigators will use MCC measurements to determine the durability of action of hypertonic saline in healthy (i.e. non-CF) subjects. 2. The investigators will determine the intra- and inter-individual variability of baseline MCC measurements using a slow inhalation/large particle protocol in healthy subjects to guide future sample size calculations.
Interventions
DEVICEHypertonic Saline
2.8% NaCl x 4ml via nebulizer
Sponsors
Gilead Sciences
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects completed mucociliary clearance measurements (via gamma scintigraphy) at baseline, 30 minutes after inhaling 2.8% NaCl, and 4 hours after inhaling 2.8% NaCl at separate study visits to characterize acute vs. sustained effects of inhaled 2.8% NaCl on this physiologic process.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects, without respiratory or cardiac comorbidities * Age 18-55 years, inclusive * FEV1 \> 80% predicted and FEV1/FVC ratio \>70% * Non-pregnant female subjects must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate double-barrier method (such as a diaphragm and condom); or, must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation * Subjects who are capable of providing their written informed consent to participate in the study
Exclusion criteria
* History of smoking \> 10 pack-years * Any history of smoking within 60 days of screening * Acute upper or lower respiratory illness within 30 days of screening * Respiratory medication for any indication within 30 days of screening * History of asthma, chronic bronchitis, or other chronic lung disease * History of intolerance to hypertonic saline * Women who are pregnant, lactating, or of childbearing potential who are unwilling to use an acceptable method of contraception throughout the duration of the study. * Any condition that, in the opinion of the investigator, would potentially jeopardize the safety of the participant or the integrity of the study * History of radiation exposure within the past year that would cause the subject to exceed limits for adults established by Federal Regulations * Subjects who, in the opinion of the Principal Investigator, should not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Whole Lung Mucociliary Clearance | 30 minutes and 4 hours after inhalation | The primary outcome of mucociliary clearance (MCC) will be depicted by calculating the average rate of isotope clearance (%) from the whole lung compartment, measured for 90 minutes after isotope inhalation (MCC-Ave 90), using data points collected every 10 minutes. Absolute change in MCC-Ave90 from baseline reported for each arm |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hypertonic Saline 2.8% NaCl
Hypertonic Saline: 2.8% NaCl x 4ml via nebulizer | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Hypertonic Saline |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 31.5 years |
| Current Smoker | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants |
| Race/Ethnicity, Customized Other, Specify | 0 Participants |
| Race/Ethnicity, Customized West Asian | 0 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change in Whole Lung Mucociliary Clearance
The primary outcome of mucociliary clearance (MCC) will be depicted by calculating the average rate of isotope clearance (%) from the whole lung compartment, measured for 90 minutes after isotope inhalation (MCC-Ave 90), using data points collected every 10 minutes. Absolute change in MCC-Ave90 from baseline reported for each arm
Time frame: 30 minutes and 4 hours after inhalation
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acute Hypertonic Saline Effect | Change in Whole Lung Mucociliary Clearance | 0.6 % Clearance | Standard Deviation 6.4 |
| Sustained Hypertonic Saline Effect | Change in Whole Lung Mucociliary Clearance | -4.0 % Clearance | Standard Deviation 5.5 |
Comparison: Paired t-test performed. Null hypothesis is that no difference in clearance 30 min and 4 hr after HS inhalation existsp-value: <0.05t-test, 2 sided