Imaging Airway Liquid Absorption in Cystic Fibrosis

NCT ID: NCT01486199

Last Updated: 2017-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-10-31

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CF pediatric

In the pediatric arm 10 CF subjects ages 6-14 will perform absorptive clearance scans at baseline and at t=2 years.

Group Type: EXPERIMENTAL

Absorptive clearance scan

Intervention Type: OTHER

Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.

Controls adult

In the adult control arm 10 healthy adult subjects will perform a single absorptive clearance scan.

Group Type: EXPERIMENTAL

Absorptive clearance scan

Intervention Type: OTHER

Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.

Interventions

Absorptive clearance scan

Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Tim Corcoran

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tim Corcoran, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27009167 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24743971 (View on PubMed)

Related Links

https://www.dom.pitt.edu/paccm/faculty_info.aspx/Corcoran5127

Dr. Corcoran's University Webpage

Other Identifiers

R01HL108929

Identifier Type: NIH

Identifier Source: secondary_id

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1R01HL108929-01

Identifier Type: NIH

Identifier Source: org_study_id

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