Clinical trial NCT01887197: Repeatability and Response Study of Absorptive Clearance Scans
Official title: Repeatability and Response Study of Absorptive Clearance Scans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
mucociliary clearance
airway surface liquid
nuclear medicine
mannitol
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2013-06-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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 diethylene triamine pentaacetic 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 determine whether the imaging technique will demonstrate similar results when it is repeated on different days. They will also determine how their results change when subjects utilize several common CF medications.

Detailed description: Cystic Fibrosis (CF) is an autosomal recessive genetic disease, caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that impairs ion transport at epithelial surfaces. This results in the accumulation of dehydrated secretions in the airways and chronic infection and inflammation in the lungs, leading to significant morbidity and mortality. The investigators understanding of CF pathogenesis has increased substantially and many new targeted therapies are being developed to treat this disease, however, the measurements of clinical efficacy used to evaluate these therapies require long trials to demonstrate an effect. New translational techniques are needed to assess changes in the most basic aspects of the disease and allow for the rapid screening of disease-altering therapies. The investigators have recently developed a novel aerosol-based imaging technique to measure liquid absorption in the airways - a central pathophysiological process related to CFTR dysfunction. The investigators propose that airway liquid hyper-absorption is a key link between cellular defects in ion and fluid transport and progressive airway dysfunction in CF. Thus The investigators technique may provide a measure of disease severity and rapid indication of therapeutic correction in advance of currently available outcome measures.

Eligibility criteria: Inclusion Criteria:

* subjects 18 years old or older with a diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms who are clinically stable as determined by a physician co-investigator

Exclusion Criteria:

* one second forced expiratory volume (FEV1) \<50% of predicted
* nursing mother
* positive urine pregnancy test or unwilling to test
* cigarette smoker
* unwilling to stop hypertonic saline therapy for 72 hours prior to each test day
* are intolerant to hypertonic saline (response only)
* are intolerant to any inhaled therapies (response only)
* fail mannitol tolerance testing (response only)
* have a history of excessive (uncontrollable) coughing after an osmotic stimulus (response only)
* have a history of hemoptysis (response only)

Primary outcomes:
measure: absorptive clearance variability
timeFrame: 30 days
measure: absorptive clearance response
timeFrame: 14 day
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Tim Corcoran, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corcoran TE, Thomas KM, Brown S, Myerburg MM, Locke LW, Pilewski JM. Liquid hyper-absorption as a cause of increased DTPA clearance in the cystic fibrosis airway. EJNMMI Res. 2013 Feb 27;3(1):14. doi: 10.1186/2191-219X-3-14.
citation: Corcoran TE, Thomas KM, Myerburg MM, Muthukrishnan A, Weber L, Frizzell R, Pilewski JM. Absorptive clearance of DTPA as an aerosol-based biomarker in the cystic fibrosis airway. Eur Respir J. 2010 Apr;35(4):781-6. doi: 10.1183/09031936.00059009. Epub 2009 Aug 28.
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.