Absorptive Clearance in the Cystic Fibrosis Airway

NCT00541190 | Completed Results DMC

• 2 other identifiers: PRO07060240NIH K25 HL081533-02
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this overall project is to develop a new aerosol-based technique for quantifying liquid absorption in the airways of subjects with cystic fibrosis(CF) that can be used to help develop new therapies. In CF, mutations in the CF gene result in dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ion channel on the cells that line the airway epithelium, causing improper fluxes of ions such as sodium, chloride, and bicarbonate. The so called "low volume" hypothesis of CF pathogenesis contends that abnormal absorption of ions from the airways causes excessive absorption of liquid, resulting in an airway surface liquid layer that is dehydrated and difficult to clear. Here we are measuring the absorption rate of a radiolabeled small molecule (DTPA) from the lungs of cystic fibrosis patients and healthy controls. We hypothesize that the molecule will absorb more quickly in cystic fibrosis patients. Further studies will be performed to determine if DTPA absorption is related to liquid absorption in the airways.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; mucociliary clearance; outcome measures

Outcome Measures

Primary Outcomes (1)

• Absorptive Clearance Rate

  The absorptive clearance rate is the percentage of the radiolabeled small molecule DTPA that is cleared through absorption over a 60 minute period. Total DTPA clearance includes absorptive and mucociliary components. The mucociliary component is determined by measuring the clearance of a radiolabeled particle over the same period (Technetium 99m sulfur colloid; Tc-SC), and subtracted from total DTPA clearance in order to determine the absorptive component. Here we specifically report absorption from the central lung zone to capture the behavior within the airways.

  single measurement

Secondary Outcomes (1)

• Mucociliary Clearance Rate

  single measurement

Study Arms (2)

cystic fibrosis

EXPERIMENTAL

Cystic fibrosis patients

Other: Technetium [Tc-99m] sulfur colloid and Indium [In-111] DTPA

healthy controls

EXPERIMENTAL

Healthy control subjects

Other: Technetium [Tc-99m] sulfur colloid and Indium [In-111] DTPA

Interventions

Technetium [Tc-99m] sulfur colloid and Indium [In-111] DTPA OTHER

Subjects perform a single nuclear medicine scan after inhaling an aerosol containing Technetium 99m sulfur colloid and Indium 111 DTPA.

cystic fibrosis; healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cystic fibrosis subjects and healthy controls
• Age ≥ 18 years
• Diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms (CF subjects)
• Clinically stable as determined by the investigator (pulmonologist)

You may not qualify if:

• Reactive airways disease
• Tobacco smokers (regular smoking within 6 months of enrollment)
• Positive urine pregnancy test on the day of testing
• FEV1p value of \< 50%
• SaO2 \< 92%, or if they require supplemental oxygen.
• Subjects performing other radioisotope studies within the last 2 weeks will be excluded.
• Healthy subjects with any history of lung disease will be excluded.
• Women currently breastfeeding
• Subjects not willing to stop treatments with inhaled hypertonic saline for 48 hours in advance of the study.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• 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.

  PMID: 27009167 DERIVED

• 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.

  PMID: 19717485 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Technetium; Indium; Indium-111; Pentetic Acid

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Transition Elements; Radioisotopes; Isotopes; Metals; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Results Point of Contact

• Title: Tim Corcoran
• Organization: University of Pittsburgh

corcorante@upmc.edu

412-624-8918

Study Officials

• Timothy E Corcoran, Ph.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 10, 2007
• Study Start: October 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: August 24, 2017
• Results First Posted: February 3, 2012

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)