- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01223183
Absorptive Clearance After Inhaled Osmotics in Cystic Fibrosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
There is a substantial need for new biomarkers in the study of cystic fibrosis (CF) lung disease. Conventional endpoints, such as rate of FEV1 decline, require prolonged trials and large sample sizes to demonstrate therapeutic efficacy. Ideally such biomarkers would provide a quantitative window to the most basic aspects of CF pathophysiology, allowing for the development and evaluation of therapies prior to large scale clinical trials. The basic defect of CF lung disease occurs in the airways where dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium (ENaC) channels is thought to create an ionic gradient that causes excessive liquid absorption across the epithelium. This results in a dehydrated airway surface liquid (ASL) layer, defective mucociliary clearance, and an increased proclivity for infection and inflammation.
Aerosol-based methods have been developed to measure mucociliary clearance in the lung and used to demonstrate the efficacy of inhaled osmotic therapies. We have developed an aerosol technique to measure both mucociliary clearance and the absorptive clearance of a hydrophilic small molecule (diethylenetriaminepentaacetic acid or DTPA) in whole, central, and peripheral lung regions. We estimate DTPA absorption by delivering an aerosol containing both Indium 111 DTPA (In-DTPA) and Technetium 99m sulfur colloid (Tc-SC) to the airways. The clearance of each radiopharmaceutical is imaged independently and two separate clearance curves are calculated. In-DTPA is cleared through both absorption and mucociliary clearance while Tc-SC is cleared only through the mucociliary route. The difference between the clearance rates of the radiopharmaceuticals provides an estimate of In-DTPA absorption rate.
Our previous studies have demonstrated that absorption of In-DTPA occurs at a higher rate in central (airway dominated) lung zones of CF subjects compared to controls (42 vs. 32 %/hr, CF n= 9, control n=10, p=0.03). We believe that this increased In-DTPA absorption is being caused by the increased liquid absorption occurring in these airways, however there are other potential causes such as increase in tight junction permeability or epithelial denuding.
In this study we propose to measure In-DTPA absorption after the delivery of interventions known to affect liquid absorption in the airways to see if changes in In-DTPA absorption mirror the changes in liquid absorption known to be caused by the interventions.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- age ≥ 18 years
- diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms
- clinically stable as determined by the investigator (pulmonologist)
Exclusion Criteria:
- intolerant to hypertonic saline.
- FEV1%p <40% of predicted
- nursing mother
- positive urine pregnancy test
- unwilling to stop hypertonic saline therapy for 72 hours prior to each test day
- cigarette smoker (regular smoking within 6 months of study)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: isotonic saline then hypertonic saline
Subjects inhaled nebulized isotonic saline on study day 1, and then after a 5-24 day washout period, subjects inhaled nebulized 7% hypertonic saline on study day 2.
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single treatment by inhalation
single treatment by inhalation
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ACTIVE_COMPARATOR: hypertonic saline then isotonic saline
Subjects inhaled nebulized 7% hypertonic saline on study day 1, and then after a 5-24 day washout period, subjects inhaled nebulized isotonic saline on study day 2.
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single treatment by inhalation
single treatment by inhalation
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absorptive Clearance Rate After Isotonic Saline Inhalation
Time Frame: 80 minutes after radiopharmaceutical inhalation
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The absorption rate of Indium 111 diethylenetriaminepentaacetic acid (In-DTPA) in the airways after the inhalation of isotonic saline
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80 minutes after radiopharmaceutical inhalation
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Absorptive Clearance Rate After Hypertonic Saline Inhalation
Time Frame: 80 minutes after radiopharmaceutical inhalation
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The absorption rate of In-DTPA after the inhalation of hypertonic saline
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80 minutes after radiopharmaceutical inhalation
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Mucociliary Clearance Rate After Isotonic Saline Inhalation
Time Frame: 80 minutes after radiopharmaceutical inhalation
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The clearance rate of Tc-SC after the inhalation of isotonic saline
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80 minutes after radiopharmaceutical inhalation
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Mucociliary Clearance Rate After Hypertonic Saline Inhalation
Time Frame: 80 minutes after radiopharmaceutical inhalation
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The clearance rate of Tc-SC after the inhalation of hypertonic saline
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80 minutes after radiopharmaceutical inhalation
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tim Corcoran, PhD, University of Pittsburgh
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO09080375
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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