Cystic FibrosisPhase 1NCT01223183
Absorptive Clearance After Inhaled Osmotics in Cystic Fibrosis
A Phase 1 study testing hypertonic saline (7%) and isotonic saline in people with Cystic Fibrosis, run by University of Pittsburgh at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- hypertonic saline (7%) and isotonic saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Dec 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Being tested
- hypertonic saline (7%), isotonic saline
- Keywords
- cystic fibrosis, nuclear medicine, aerosol, nebulizer
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypertonic saline (7%)Drug
single treatment by inhalation
isotonic salineDrug
single treatment by inhalation
| Study group | Role | What they receive |
|---|---|---|
| isotonic saline then hypertonic saline | Active comparator | 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. Receives: Drug: hypertonic saline (7%); Drug: isotonic saline |
| hypertonic saline then isotonic saline | Active comparator | 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. Receives: Drug: hypertonic saline (7%); Drug: isotonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absorptive Clearance Rate After Isotonic Saline Inhalation
The absorption rate of Indium 111 diethylenetriaminepentaacetic acid (In-DTPA) in the airways after the inhalation of isotonic saline
Measured: 80 minutes after radiopharmaceutical inhalation
Absorptive Clearance Rate After Hypertonic Saline Inhalation
The absorption rate of In-DTPA after the inhalation of hypertonic saline
Measured: 80 minutes after radiopharmaceutical inhalation
Mucociliary Clearance Rate After Isotonic Saline Inhalation
The clearance rate of Tc-SC after the inhalation of isotonic saline
Measured: 80 minutes after radiopharmaceutical inhalation
Mucociliary Clearance Rate After Hypertonic Saline Inhalation
The clearance rate of Tc-SC after the inhalation of hypertonic saline
Measured: 80 minutes after radiopharmaceutical inhalation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tim Corcoran, University of Pittsburgh
- Investigators
- Tim Corcoran, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01223183
- Sponsor's protocol ID
- PRO09080375
- Status last verified
- Nov 2018
- First submitted
- 14 Oct 2010
- Last updated
- 29 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
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.
PubMed 19717485Locke 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.
PubMed 24743971Locke 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.
PubMed 27009167
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Absorptive Clearance After Inhaled Osmotics in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT01223183
- Acronym / sponsor ID
- PRO09080375
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis, nuclear medicine, aerosol, nebulizer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Posted 5 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| isotonic saline then hypertonic saline | Active comparator | Drug: hypertonic saline (7%), Drug: isotonic salineSubjects 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. |
| hypertonic saline then isotonic saline | Active comparator | Drug: hypertonic saline (7%), Drug: isotonic salineSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypertonic saline (7%)single treatment by inhalation | Drug | hypertonic saline then isotonic saline, isotonic saline then hypertonic saline |
| isotonic salinesingle treatment by inhalation | Drug | hypertonic saline then isotonic saline, isotonic saline then hypertonic saline |
Primary outcome
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19717485Corcoran 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.
- Results publication: PubMed 24743971Locke 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.
- Derived from this study: PubMed 27009167Locke 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Corcoran, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing hypertonic saline (7%) and isotonic saline in people with Cystic Fibrosis, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absorptive Clearance Rate After Isotonic Saline Inhalation (time frame: 80 minutes after radiopharmaceutical inhalation). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01223183, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2018.