Cystic Fibrosis
Conditions
Keywords
cystic fibrosis, mucociliary clearance, outcome measures
Brief summary
The objective of this overall project is to develop a new aerosol-based technique for quantifying liquid absorption in the airways of subjects with cystic fibrosis(CF) that can be used to help develop new therapies. In CF, mutations in the CF gene result in dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ion channel on the cells that line the airway epithelium, causing improper fluxes of ions such as sodium, chloride, and bicarbonate. The so called low volume hypothesis of CF pathogenesis contends that abnormal absorption of ions from the airways causes excessive absorption of liquid, resulting in an airway surface liquid layer that is dehydrated and difficult to clear. Here we are measuring the absorption rate of a radiolabeled small molecule (DTPA) from the lungs of cystic fibrosis patients and healthy controls. We hypothesize that the molecule will absorb more quickly in cystic fibrosis patients. Further studies will be performed to determine if DTPA absorption is related to liquid absorption in the airways.
Interventions
OTHERTechnetium [Tc-99m] sulfur colloid and Indium [In-111] DTPA
Subjects perform a single nuclear medicine scan after inhaling an aerosol containing Technetium 99m sulfur colloid and Indium 111 DTPA.
Sponsors
University of Pittsburgh
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Cystic fibrosis subjects and healthy controls * Age ≥ 18 years * Diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms (CF subjects) * Clinically stable as determined by the investigator (pulmonologist)
Exclusion criteria
* Reactive airways disease * Tobacco smokers (regular smoking within 6 months of enrollment) * Positive urine pregnancy test on the day of testing * FEV1p value of \< 50% * SaO2 \< 92%, or if they require supplemental oxygen. * Subjects performing other radioisotope studies within the last 2 weeks will be excluded. * Healthy subjects with any history of lung disease will be excluded. * Women currently breastfeeding * Subjects not willing to stop treatments with inhaled hypertonic saline for 48 hours in advance of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absorptive Clearance Rate | single measurement | The absorptive clearance rate is the percentage of the radiolabeled small molecule DTPA that is cleared through absorption over a 60 minute period. Total DTPA clearance includes absorptive and mucociliary components. The mucociliary component is determined by measuring the clearance of a radiolabeled particle over the same period (Technetium 99m sulfur colloid; Tc-SC), and subtracted from total DTPA clearance in order to determine the absorptive component. Here we specifically report absorption from the central lung zone to capture the behavior within the airways. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mucociliary Clearance Rate | single measurement | Mucociliary clearance rate represents the rate at which the lungs clear an inhaled particulate. Here it specifically represents the percentage of inhaled Technetium 99m sulfur colloid cleared from the lungs over a 60 minute period. This is reported based on whole lung areas to allow comparisons with previous studies. |
Countries
United States
Participant flow
Recruitment details
Cystic fibrosis subjects were recruited during normal clinical visits. Healthy control subjects were recruited using posted advertisement.
Pre-assignment details
All enrolled subjects performed a single nuclear medicine imaging study.
Participants by arm
| Arm | Count |
|---|---|
| Cystic Fibrosis Cystic fibrosis patients | 10 |
| Healthy Controls Healthy subjects. | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Healthy Controls | Cystic Fibrosis | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 21 Participants |
| Age, Continuous | 29 years STANDARD_DEVIATION 7 | 29 years STANDARD_DEVIATION 11 | 29 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 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 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Absorptive Clearance Rate
The absorptive clearance rate is the percentage of the radiolabeled small molecule DTPA that is cleared through absorption over a 60 minute period. Total DTPA clearance includes absorptive and mucociliary components. The mucociliary component is determined by measuring the clearance of a radiolabeled particle over the same period (Technetium 99m sulfur colloid; Tc-SC), and subtracted from total DTPA clearance in order to determine the absorptive component. Here we specifically report absorption from the central lung zone to capture the behavior within the airways.
Time frame: single measurement
Population: No formal power analysis was performed for this pilot study. Two subjects (one CF, one control) were identified as obvious outliers with whole lung Tc-SC clearance rates more than two standard deviations above the average of the group. These outliers were excluded from further analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystic Fibrosis | Absorptive Clearance Rate | 42 percentage of DTPA absoprtion per hour | Standard Deviation 11 |
| Healthy Controls | Absorptive Clearance Rate | 32 percentage of DTPA absoprtion per hour | Standard Deviation 7 |
Secondary
Mucociliary Clearance Rate
Mucociliary clearance rate represents the rate at which the lungs clear an inhaled particulate. Here it specifically represents the percentage of inhaled Technetium 99m sulfur colloid cleared from the lungs over a 60 minute period. This is reported based on whole lung areas to allow comparisons with previous studies.
Time frame: single measurement
Population: No formal power analysis was performed for this pilot study. Two subjects (one CF, one control) were identified as obvious outliers with whole lung Tc-SC clearance rates more than two standard deviations above the average of the group. These outliers were excluded from further analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystic Fibrosis | Mucociliary Clearance Rate | 8 percentage lung clearance per hour | Standard Deviation 4 |
| Healthy Controls | Mucociliary Clearance Rate | 7 percentage lung clearance per hour | Standard Deviation 4 |