Cystic Fibrosis
Conditions
Keywords
cystic fibrosis, surfactant, aerosol, inhaled drug, inhaled antibiotic
Brief summary
Inhaled medications are often used to treat lung diseases such as cystic fibrosis. We are performing this study to determine whether inhaled medications dissolved in surfactant-based solutions will distribute more evenly throughout the lungs when compared to standard saline-based solutions. We think that inhaling medication that is in a surfactant-based liquid will result in more medication reaching partially blocked parts of the lung. This study will use a special nuclear medicine test called an aerosol deposition scan to compare how a drug spreads in the lung using a surfactant-based aerosol compared to a saline-based aerosol.
Detailed description
Cystic fibrosis (CF) is an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the United States (70,000 worldwide). The lungs of a person with cystic fibrosis often contain thick sticky mucus that can clog the lungs and lead to life-threatening lung infections. A major milestone in the treatment of CF was the development of an inhaled form of an antibiotic drug called tobramycin. For an inhaled antibiotic to work it must be delivered to all infected parts of the lung. Many studies have shown that blockages in the lungs, like those found in CF patients, can prevent inhaled medicines from reaching all parts of the lungs. Usually aerosolized medications are dissolved in saline or water. Most of these medications could be dissolved in surfactant solutions and aerosolized. Soaps are common examples of surfactants. Surfactants may have the ability to spread medication over the inside surface of the lungs similar to the way dish soap spreads over water. We think that inhaling medication that is in a surfactant-based liquid will result in more medication reaching partially blocked parts of the lung. We further believe that the normal movements of the lung associated with breathing will further spread surfactant-based aerosol medications, and contribute to even more even drug distribution over longer periods of time. A surfactant-based inhaled antibiotic would have the potential to reach more sites of infection in the lung, possibly getting rid of infection all together. This study will use a special test called an aerosol deposition scan to compare how a drug spreads in the lung using a surfactant-based aerosol compared to a saline-based aerosol. The study includes one screening and two testing visits.
Interventions
DRUGcalfactant
single inhaled dose by nebulizer
DRUGisotonic saline
single inhaled dose by nebulizer
Sponsors
Cystic Fibrosis Foundation
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms * Clinically stable as determined by the investigator (pulmonologist).
Exclusion criteria
* Known allergies to any of the administered components (as described by subjects or based on positive RAST test to bovine serum albumin) * Any past instances of bronchospasm associated with aerosol medications * FEV1 \< 60% predicted * Positive urine pregnancy test (as administered to all female subjects of childbearing potential on testing days) * Currently a nursing mother * History of reactive airways disease associated with significant instances of bronchoconstriction * Self-reported smoking history within the last 6 months. * Subjects receiving any treatments or diagnostic procedures involving radioisotopes within the last 30 days. * Subjects in the CF arm of the study will also be excluded if their pre-study pulmonary function test (FEV1) is more than 15% depressed from their last baseline pulmonary function test, if this baseline value is from within the last 6 months, or if they have experienced an exacerbation requiring hospitalization or treatment with an IV antibiotic within the last month.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Uniformity of Aerosol Distribution | 30 minutes | Measured change in central/peripheral (c/p) dose ratio over a 30 minute period after aersol delivery (c/p at t=30 - c/p at t=0). Central and peripheral lung doses are measured as radioactive counts depicted on nuclear medicine gamma camera images after radioisotope aerosol delivery. The central lung zone is a rectangle with 1/2 the height and 1/2 the width of a box outlining the whole right lung. The peripheral lung zone is defined as the portion of the lung outside of the central lung zone. A change in c/p ratio over time would indicate transport of material from one lung zone to the other. The variable represents the realtive proportion of airways dosing to alveolar dosing - an indication of deposition uniformity in the lungs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Lung Dose | 30 minutes after delivery | Change over 30 minutes in the percentage of the total deposited aerosol dose found in the peripheral lung zone. We are reporting the %peripheral dose at t=30 minus the %peripheral dose at t=0. This dose is determined based on measured radioactive counts after aerosol delivery, using nuclear medicine gamma camera images. The central lung zone is defined as a rectangle with 1/2 the height and 1/2 the width of a rectangle that surrounds the right whole lung. The peripheral zone is the portion of the lung image not included in the central lung zone. |
Countries
United States
Participant flow
Recruitment details
Eight subjects with cystic fibrosis were recruited.
Pre-assignment details
Subjects performed two imaging study days. On one study day subjects inhaled Tc-SC particles suspended in calfactant. On the other study day they inhaled the same particles in saline. The order of the study days was randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cystic Fibrosis Subjects Subjects with cystic fibrosis
isotonic saline aerosol : single inhaled dose, 3ml by nebulizer
calfactant aerosol : single inhaled dose, 3ml by nebulizer | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Cystic Fibrosis Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 28 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Uniformity of Aerosol Distribution
Measured change in central/peripheral (c/p) dose ratio over a 30 minute period after aersol delivery (c/p at t=30 - c/p at t=0). Central and peripheral lung doses are measured as radioactive counts depicted on nuclear medicine gamma camera images after radioisotope aerosol delivery. The central lung zone is a rectangle with 1/2 the height and 1/2 the width of a box outlining the whole right lung. The peripheral lung zone is defined as the portion of the lung outside of the central lung zone. A change in c/p ratio over time would indicate transport of material from one lung zone to the other. The variable represents the realtive proportion of airways dosing to alveolar dosing - an indication of deposition uniformity in the lungs.
Time frame: 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Inhaling Saline | Uniformity of Aerosol Distribution | -0.05 ratio | Standard Deviation 0.16 |
| Subjects Inhaling Surfactant | Uniformity of Aerosol Distribution | 0.10 ratio | Standard Deviation 0.1 |
Comparison: Wilcoxon matched-pairs signed-ranks test was used for comparisonsp-value: 0.07Wilcoxon (Mann-Whitney)
Secondary
Peripheral Lung Dose
Change over 30 minutes in the percentage of the total deposited aerosol dose found in the peripheral lung zone. We are reporting the %peripheral dose at t=30 minus the %peripheral dose at t=0. This dose is determined based on measured radioactive counts after aerosol delivery, using nuclear medicine gamma camera images. The central lung zone is defined as a rectangle with 1/2 the height and 1/2 the width of a rectangle that surrounds the right whole lung. The peripheral zone is the portion of the lung image not included in the central lung zone.
Time frame: 30 minutes after delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Inhaling Saline | Peripheral Lung Dose | -3 percentage of lung dose | Standard Deviation 5 |
| Subjects Inhaling Surfactant | Peripheral Lung Dose | -8 percentage of lung dose | Standard Deviation 8 |
Comparison: Wilcoxon matched-pairs signed-ranks test was used for comparisonsp-value: 0.29Wilcoxon (Mann-Whitney)