Clinical trial NCT01486199: Imaging Airway Liquid Absorption in Cystic Fibrosis
Official title: Imaging Airway Liquid Absorption in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
mucociliary clearance
airway surface liquid
nuclear medicine
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-12-06
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Absorptive Clearance Rate
timeFrame: study day 1
measure: Mucociliary Clearance Rate
timeFrame: study day 1
Secondary outcomes:
measure: Absorptive Clearance Rate
timeFrame: t=2 years
measure: Mucociliary Clearance Rate
timeFrame: t=2 years, measure made 80 minutes after radiopharmaceutical inhalation
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Tim Corcoran, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Locke LW, Myerburg MM, Weiner DJ, Markovetz MR, Parker RS, Muthukrishnan A, Weber L, Czachowski MR, Lacy RT, Pilewski JM, Corcoran TE. Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung. Eur Respir J. 2016 May;47(5):1392-401. doi: 10.1183/13993003.01880-2015. Epub 2016 Mar 23.
citation: Locke LW, Myerburg MM, Markovetz MR, Parker RS, Weber L, Czachowski MR, Harding TJ, Brown SL, Nero JA, Pilewski JM, Corcoran TE. Quantitative imaging of airway liquid absorption in cystic fibrosis. Eur Respir J. 2014 Sep;44(3):675-84. doi: 10.1183/09031936.00220513. Epub 2014 Apr 17.