Imaging Airway Liquid Absorption in Cystic Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Absorptive clearance scan

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CF pediatric; In the pediatric arm 10 CF subjects ages 6-14 will perform absorptive clearance scans at baseline and at t=2 years.	Other: Absorptive clearance scan; Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.
Experimental: Controls adult; In the adult control arm 10 healthy adult subjects will perform a single absorptive clearance scan.	Other: Absorptive clearance scan; Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absorptive Clearance Rate	Absorptive clearance rate measured 80 minutes after radiopharmaceutical inhalation. Absorptive clearance is the absorptive component of the clearance of Indium 111-diethylenetriaminepentaacetic acid (In-DTPA) from the lungs.	study day 1
Mucociliary Clearance Rate	Mucociliary clearance rate measured 80 minutes after radiopharmaceutical inhalation. Mucociliary clearance rate is the rate of clearance of Technetium sulfur colloid (Tc-SC) from the lungs.	study day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absorptive Clearance Rate	Absorptive Clearance Rate measured 80 minutes after radiopharmaceutical inhalation. Absorptive clearance is the absorptive component of the clearance of In-DTPA from the lungs.	t=2 years
Mucociliary Clearance Rate	Mucociliary clearance rate measured 80 minutes after radiopharmaceutical inhalation. Mucociliary clearance rate is the rate of clearance of Technetium sulfur colloid (Tc-SC) from the lungs.	t=2 years, measure made 80 minutes after radiopharmaceutical inhalation

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Tim Corcoran, Ph.D., University of Pittsburgh

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Dr. Corcoran's University Webpage

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: November 18, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: cystic fibrosis; mucociliary clearance; nuclear medicine; airway surface liquid
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 1R01HL108929-01 (U.S. NIH Grant/Contract); R01HL108929 (U.S. NIH Grant/Contract)