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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL108929-01 | U.S. NIH Grant/Contract | View source |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Repeatability | Experimental | Subjects perform two sequential absorptive clearance scans (within 30 days) to determine the repeatability of the technique. Subjects also perform a third scan two years later so that longitudinal change can be measured. |
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| Response | Experimental | Subjects perform three different absorptive clearance scans. One is a baseline measurement while the other two measure absorptive clearance after an intervention (inhaled hypertonic saline, mannitol inhalation powder). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Absorptive clearance scan | Other | Subjects inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m sulfur colloid. |
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| Measure | Description | Time Frame |
|---|---|---|
| absorptive clearance variability | The difference in absorptive clearance measured on two different study days in the same subjects as an indicator of measurement variability | 30 days |
| absorptive clearance response | The change in absorptive clearance demonstrated in response to therapy when compared to baseline | 14 day |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tim Corcoran, Ph.D. | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23446051 | Background | 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. | |
| 19717485 | Background | 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. |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D008353 | Mannitol |
| ID | Term |
|---|---|
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D002241 | Carbohydrates |
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| inhaled hypertonic saline (7%) | Drug | nebulized hypertonic saline (7%) |
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| mannitol inhalation powder | Drug | mannitol inhalation powder |
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| 27009167 | Derived | 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. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |