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Absorptive Clearance After Inhaled Osmotics in Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT01223183
Recruitment Status : Completed
First Posted : October 18, 2010
Results First Posted : February 5, 2018
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Tim Corcoran, University of Pittsburgh

Brief Summary:
Blockage of the breathing tubes of the lungs by thick, sticky mucus is a major cause of lung problems for people with cystic fibrosis (CF). Many researchers now believe that people with CF absorb too much water from the insides of their lungs, and that the mucus in their lungs becomes so thick and sticky because there is not enough water in it. The investigators are trying to develop ways to measure how fast water is absorbed from the breathing tubes in the lung so that the investigators can more quickly test new medications that are being developed to fix this problem for CF patients. The investigators have already done studies showing that people with CF absorb a particular radioactive drug (Indium-111 diethylenetriaminepentaacetic acid or In-DTPA) from their lungs more quickly than people without CF. Now the investigators are trying to prove that the absorption of this drug is related to the absorption of water. The investigators measure the absorption of In-DTPA by delivering it in an aerosol (inhaled mist) along with another radioactive drug (Technetium 99m sulfur colloid or Tc-SC). This other drug helps us measure how much material is cleared from the lungs in other ways (like coughing) without being absorbed. In this study, the investigators will measure how the absorption of In-DTPA is affected by inhaling isotonic saline and hypertonic saline (salt water), both of which the investigators know affect the absorption of water in the airways.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: hypertonic saline (7%) Drug: isotonic saline Phase 1

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 : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Subjects inhale isotonic saline on one imaging day and 7% hypertonic on the other. The order is randomized. There is a period of 5-24 days between imaging days.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Absorptive Clearance After Inhaled Osmotics in Cystic Fibrosis
Study Start Date : September 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
U.S. FDA Resources

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.
Drug: hypertonic saline (7%)
single treatment by inhalation
Drug: isotonic saline
single treatment by inhalation
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.
Drug: hypertonic saline (7%)
single treatment by inhalation
Drug: isotonic saline
single treatment by inhalation



Primary Outcome Measures :
  1. Absorptive Clearance Rate After Isotonic Saline Inhalation [ Time Frame: 80 minutes after radiopharmaceutical inhalation ]
    The absorption rate of Indium 111 diethylenetriaminepentaacetic acid (In-DTPA) in the airways after the inhalation of isotonic saline

  2. Absorptive Clearance Rate After Hypertonic Saline Inhalation [ Time Frame: 80 minutes after radiopharmaceutical inhalation ]
    The absorption rate of In-DTPA after the inhalation of hypertonic saline

  3. Mucociliary Clearance Rate After Isotonic Saline Inhalation [ Time Frame: 80 minutes after radiopharmaceutical inhalation ]
    The clearance rate of Tc-SC after the inhalation of isotonic saline

  4. Mucociliary Clearance Rate After Hypertonic Saline Inhalation [ Time Frame: 80 minutes after radiopharmaceutical inhalation ]
    The clearance rate of Tc-SC after the inhalation of hypertonic saline



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01223183


Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Tim Corcoran, PhD University of Pittsburgh

Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tim Corcoran, PhD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01223183     History of Changes
Other Study ID Numbers: PRO09080375
First Posted: October 18, 2010    Key Record Dates
Results First Posted: February 5, 2018
Last Update Posted: February 5, 2018
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Tim Corcoran, University of Pittsburgh:
cystic fibrosis
nuclear medicine
aerosol
nebulizer

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases