Self-dispersing Liquids as Aerosol Drug Carriers

Study Overview
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Brief Summary
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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
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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.

Official Title
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Self-dispersing Liquids as Aerosol Drug Carriers

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: calfactant
* Drug: isotonic saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Subjects inhaled calfactant then isotonic saline | Drug: calfactant<br>* single inhaled dose by nebulizer<br>* Other names: Infasurf;Drug: isotonic saline<br>* single inhaled dose by nebulizer<br>|
| Experimental: 2<br>Subjects inhaled isotonic saline then calfactant | Drug: calfactant<br>* single inhaled dose by nebulizer<br>* Other names: Infasurf;Drug: isotonic saline<br>* single inhaled dose by nebulizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 minutes after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, surfactant, aerosol, inhaled drug, inhaled antibiotic