Imaging Airway Liquid Absorption in Cystic Fibrosis

Study Overview
=================
Brief Summary
-----------------
The investigators are developing a new nuclear medicine imaging technique for measuring liquid absorption in the airways that can be applied to screen new medications being developed to treat cystic fibrosis (CF). The investigators believe that the absorption of the small molecule radiopharmaceutical Indium 111-diethylenetriaminepentaacetic acid (In-DTPA) will indicate changes in liquid absorption in the airways and demonstrate whether new CF medications will be effective. In this study the investigators will further develop this technique through testing involving pediatric CF patients and healthy control subjects.

Detailed Description
-----------------
The investigators have recently developed a novel aerosol-based imaging technique to detect changes in liquid absorption in the airways - a central pathophysiological process known to be important in cystic fibrosis (CF) lung disease. This technique may provide a measure of disease severity and indication of therapeutic correction in advance of currently available outcome measures. It involves the simultaneous delivery of two radiopharmaceuticals by inhalation: one an absorbable small-molecule (Indium-111 labeled diethylenetriaminepentaacetic acid; In-DTPA) and the other a non-absorbable particle (Technetium 99m labeled sulfur colloid; Tc-SC). The overarching hypothesis is that In-DTPA absorption provides a quantifiable, non-invasive measurement of airway liquid absorption that (a) is sensitive to CF genotype, (b) uniquely identifies basic disease phenotype and predicts disease severity, and (c) is modulated by therapeutic interventions.

Official Title
-----------------
Imaging Airway Liquid Absorption in Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Other: Absorptive clearance scan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult healthy control arm: subjects 18 years old or older without a diagnosis of lung disease. Pediatric CF arm: subjects 6-14 years with a diagnosis of cystic fibrosis as determined by sweat test or genotype subjects who are clinically stable as determined by the pediatrician co-investigator subjects must have a previously demonstrated ability to perform reproducible pulmonary function testing based on previous clinical visits. Females in all groups who are of child-bearing potential will need to have a negative urine pregnancy test. Exclusion Criteria: Adult healthy control arm: FEV1%p < 80% of predicted nursing mother positive urine pregnancy test or unwilling to test cigarette smoker (regular smoking within 6 months of study). Pediatric CF arm: FEV1%p < 40% of predicted nursing mother positive urine pregnancy test for females of childbearing potential unable or unwilling to comply with test procedure cigarette smoker (regular smoking within 6 months of study). Subjects unable to lie recumbent without moving for the 80 minute imaging period will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 6 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CF pediatric<br>In the pediatric arm 10 CF subjects ages 6-14 will perform absorptive clearance scans at baseline and at t=2 years. | Other: Absorptive clearance scan<br>* Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.<br>|
| Experimental: Controls adult<br>In the adult control arm 10 healthy adult subjects will perform a single absorptive clearance scan. | Other: Absorptive clearance scan<br>* Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorptive Clearance Rate | Absorptive clearance rate measured 80 minutes after radiopharmaceutical inhalation. Absorptive clearance is the absorptive component of the clearance of Indium 111-diethylenetriaminepentaacetic acid (In-DTPA) from the lungs. | study day 1 | 
| Mucociliary Clearance Rate | Mucociliary clearance rate measured 80 minutes after radiopharmaceutical inhalation. Mucociliary clearance rate is the rate of clearance of Technetium sulfur colloid (Tc-SC) from the lungs. | study day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorptive Clearance Rate | Absorptive Clearance Rate measured 80 minutes after radiopharmaceutical inhalation. Absorptive clearance is the absorptive component of the clearance of In-DTPA from the lungs. | t=2 years | 
| Mucociliary Clearance Rate | Mucociliary clearance rate measured 80 minutes after radiopharmaceutical inhalation. Mucociliary clearance rate is the rate of clearance of Technetium sulfur colloid (Tc-SC) from the lungs. | t=2 years, measure made 80 minutes after radiopharmaceutical inhalation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cystic fibrosis, mucociliary clearance, airway surface liquid, nuclear medicine