Cystic Fibrosis
Conditions
Keywords
cystic fibrosis, mucociliary clearance, airway surface liquid, nuclear medicine
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.
Interventions
Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Pittsburgh
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absorptive Clearance Rate | study day 1 | 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. |
| Mucociliary Clearance Rate | study day 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absorptive Clearance Rate | t=2 years | Absorptive Clearance Rate measured 80 minutes after radiopharmaceutical inhalation. Absorptive clearance is the absorptive component of the clearance of In-DTPA from the lungs. |
| Mucociliary Clearance Rate | t=2 years, measure made 80 minutes after radiopharmaceutical inhalation | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CF Pediatric Cystic Fibrosis subjects ages 6-14 | 10 |
| Controls Adult Adult control subjects 18 or older | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Two Year Period Between Study Days | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | CF Pediatric | Controls Adult | Total |
|---|---|---|---|
| Age, Continuous | 10.5 years STANDARD_DEVIATION 1.5 | 31.2 years STANDARD_DEVIATION 15 | 20.9 years STANDARD_DEVIATION 14.9 |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: study day 1
Population: One pediatric subject did not deposit sufficient aerosol to be analyzed. One control subject did not perform imaging procedures after signing consent because of a low result on a screening pulmonary function testing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CF Pediatric | Absorptive Clearance Rate | 34.0 percent cleared / 80 minutes | Standard Deviation 10.4 |
| Controls Adult | Absorptive Clearance Rate | 17.7 percent cleared / 80 minutes | Standard Deviation 6.9 |
Comparison: Comparing absorptive clearance in CF children vs adult controlsp-value: 0.002t-test, 2 sided
Primary
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.
Time frame: study day 1
Population: One pediatric subject did not deposit sufficient aerosol to be analyzed. One control subject did not perform imaging procedures after signing consent because of a low result on a screening pulmonary function testing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CF Pediatric | Mucociliary Clearance Rate | 22.8 percent cleared / 80 minutes | Standard Deviation 13.7 |
| Controls Adult | Mucociliary Clearance Rate | 31.4 percent cleared / 80 minutes | Standard Deviation 13.1 |
Comparison: Comparison of mucociliary clearance in CF children compared to healthy adultsp-value: 0.2t-test, 2 sided
Secondary
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.
Time frame: t=2 years
Population: Only pediatric CF subjects performed 2 year follow-up scan. One subject did not perform the second imaging day since day one image quality was poor. Two other subjects had poor imaging data on follow up day and were therefore not included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CF Pediatric | Absorptive Clearance Rate | 28.6 percent cleared / 80 min | Standard Deviation 9.9 |
Comparison: Comparing absorptive clearance at t=0 vs t=2 years in pediatric CF subjectsp-value: 0.24Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: t=2 years, measure made 80 minutes after radiopharmaceutical inhalation
Population: Only pediatric CF subjects performed 2 year follow-up scan. One subject did not perform the second imaging day since day one image quality was poor. Two other subjects had poor imaging data on follow up day and were therefore not included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CF Pediatric | Mucociliary Clearance Rate | 22.0 percent cleared / 80 minutes | Standard Deviation 13.1 |
Comparison: Comparing mucociliary clearance at t=0 and t=2yrs in pediatric CF subjectsp-value: 0.87Wilcoxon (Mann-Whitney)