Cystic FibrosisPhase 1NCT01094704
Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis
A Phase 1 study testing sodium chloride (7%) in people with Cystic Fibrosis, run by University of North Carolina, Chapel Hill at 2 sites in United States.
Trial summary
Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. 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?
- sodium chloride (7%)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2009to May 2010
- 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
- Gender: Male or female (non-pregnant, non-lactating)
- Cystic fibrosis documented by a compatible clinical and radiographic presentation, and sweat chloride > 60 mEq/l or 2 disease causing CFTR mutations.
- Severity of Disease:
- Must have FEV1 of greater than or equal to 50% of predicted at the screening visit.
- Must have an oxygen saturation of >92% on room air as determined by pulse oximetry at the screening visit.
- Patient or legally authorized representative agrees to the patient/individual's participation in the study by signing and dating the informed consent form after the nature of the study has been fully explained and all questions have been satisfactorily answered.
Who cannot join
- Unstable lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 >15% below recent (within 6 months) clinical measurements; or a significant new finding on chest radiograph (pneumothorax, lobar/segmental collapse) not considered a part of the usual, chronic progression of CF lung disease.
- Patients unable or unwilling to be withdrawn from hypertonic saline therapy, dornase alfa, or N-acetylcysteine 3 days prior to and for the duration of each Baseline and Treatment Period will be excluded.
- Patients unable to withhold use of long-acting bronchodilators (i.e., Salmeterol, Advair, Formoterol), anti-cholinergics, and vest therapy 12 hours prior to and for the duration of each treatment period.
- Patients unable to withhold short-acting bronchodilator 6 hours prior to and for the duration of each treatment period except as prescribed by the study protocol.
- Patients that have received an investigational drug or therapy during the preceding 30 days.
- Patients that have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins University
Baltimore, Maryland, 21287
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27516
About this study
Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.
Read the detailed description
A reduction in epithelial lining fluid height in cystic fibrosis (CF) as a consequence of decreased function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel and related increased activity of the Epithelial sodium (Na) Channel (ENaC) results in impaired mucociliary clearance (MCC), mucus stasis, inflammation, infection, and ultimately progressive bronchiectasis. Inhalation of hypertonic saline (HS), through a direct osmotic effect on the airways, results in an increase in epithelial lining fluid height in vitro and an increase in MCC in vivo as measured following inhalation of a radiotracer with gamma scintigraphy (Sood, et al 2003). MCC as a biomarker is being validated in the clinic, as administration of inhaled hypertonic saline (HS) to cystic fibrosis patients results in short- and medium-term improvements in MCC (Donaldson, et al 2006), while long-term administration of HS is associated with improvements in the registration endpoints of lung function and pulmonary exacerbations (Elkins, et al 2006). Based in large part on these studies, HS has gained acceptance in the CF community, with estimates of up to 50% of patients being treated with this therapy. MCC/CC is thus an excellent choice as a Proof of Concept endpoint for exploratory clinical studies of ENaC modulators. Prior clinical experience with the ENaC blocker amiloride, which improves MCC acutely in healthy volunteers (Sood, et al 2003) but failed to improve lung function in long-term studies in CF (Pons, et al 2000), suggests that durable ENaC modulation will be required for clinical success. It is believed that modulation of ENaC for a period of at least 4 hours will be required to achieve the necessary durability. This durability should also enable twice daily dosing. For comparison we need to know the effectiveness of HS over this same period. Thus, this study is intended to assess 1) the duration of action out to 4 hours for inhaled hypertonic saline (7%) in adult CF patients and 2) the variability of MCC/CC measurements with and without HS treatment. These assessments at UNC will be compared to similar measures at Johns Hopkins University (JHU) for Novartis to determine the feasibility for future multicenter studies using MCC/CC as a primary endpoint.
- Conditions
- Cystic Fibrosis
- Being tested
- sodium chloride (7%)
- Keywords
- cystic fibrosis, mucociliary clearance, hypertonic saline
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium chloride (7%)Drug
Also called Hyper-Sal, Hypertonic saline (7%)
4mL nebulized 7% sodium chloride
| Study group | Role | What they receive |
|---|---|---|
| Hypertonic Saline - 1 hour | Experimental | sodium chloride (7%); mucociliary clearance measured 1 hour post dose Receives: Drug: sodium chloride (7%) |
| Hypertonic Saline - 4 hours | Experimental | sodium chloride (7%); mucociliary clearance measured four hours post-dose. Receives: Drug: sodium chloride (7%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Average Mucociliary Clearance (0-90 Minutes) at 1 and 4 Hrs Post Dose (MCC4hr - MCCbaseline; MCC1hr - MCCbaseline)
Duration of action of hypertonic saline as determined by measurements of mucociliary clearance/cough clearance 4 hours post dose.
Measured: 1-4 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2010 (estimated)
- Study startNov 2009
- Primary completionMay 2010
- Study completionMay 2010
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 (7)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 North Carolina, Chapel HillThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Scott Donaldson, University of North Carolina, Chapel Hill
- Investigators
- William Bennett, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01094704
- Sponsor's protocol ID
- 09-0670
- Status last verified
- Aug 2012
- First submitted
- 19 Mar 2010
- Last updated
- 21 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006 Jan 19;354(3):241-50. doi: 10.1056/NEJMoa043891.
PubMed 16421365Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
PubMed 16421364Bennett WD, Olivier KN, Zeman KL, Hohneker KW, Boucher RC, Knowles MR. Effect of uridine 5'-triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1796-801. doi: 10.1164/ajrccm.153.6.8665037.
PubMed 8665037Donaldson SH, Boucher RC. Sodium channels and cystic fibrosis. Chest. 2007 Nov;132(5):1631-6. doi: 10.1378/chest.07-0288.
PubMed 17998363Pons G, Marchand MC, d'Athis P, Sauvage E, Foucard C, Chaumet-Riffaud P, Sautegeau A, Navarro J, Lenoir G. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol. 2000 Jul;30(1):25-31. doi: 10.1002/1099-0496(200007)30:13.0.co;2-c.
PubMed 10862159Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.
PubMed 12411282Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.
PubMed 37319354
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT01094704
- Acronym / sponsor ID
- 09-0670
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis, mucociliary clearance, hypertonic saline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Johns Hopkins University, Novartis Pharmaceuticals
- Study start
- Nov 2009
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 29 Mar 2010 (estimated)
- Results
- Posted 21 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.
Detailed description
A reduction in epithelial lining fluid height in cystic fibrosis (CF) as a consequence of decreased function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel and related increased activity of the Epithelial sodium (Na) Channel (ENaC) results in impaired mucociliary clearance (MCC), mucus stasis, inflammation, infection, and ultimately progressive bronchiectasis. Inhalation of hypertonic saline (HS), through a direct osmotic effect on the airways, results in an increase in epithelial lining fluid height in vitro and an increase in MCC in vivo as measured following inhalation of a radiotracer with gamma scintigraphy (Sood, et al 2003). MCC as a biomarker is being validated in the clinic, as administration of inhaled hypertonic saline (HS) to cystic fibrosis patients results in short- and medium-term improvements in MCC (Donaldson, et al 2006), while long-term administration of HS is associated with improvements in the registration endpoints of lung function and pulmonary exacerbations (Elkins, et al 2006). Based in large part on these studies, HS has gained acceptance in the CF community, with estimates of up to 50% of patients being treated with this therapy. MCC/CC is thus an excellent choice as a Proof of Concept endpoint for exploratory clinical studies of ENaC modulators. Prior clinical experience with the ENaC blocker amiloride, which improves MCC acutely in healthy volunteers (Sood, et al 2003) but failed to improve lung function in long-term studies in CF (Pons, et al 2000), suggests that durable ENaC modulation will be required for clinical success. It is believed that modulation of ENaC for a period of at least 4 hours will be required to achieve the necessary durability. This durability should also enable twice daily dosing. For comparison we need to know the effectiveness of HS over this same period. Thus, this study is intended to assess 1) the duration of action out to 4 hours for inhaled hypertonic saline (7%) in adult CF patients and 2) the variability of MCC/CC measurements with and without HS treatment. These assessments at UNC will be compared to similar measures at Johns Hopkins University (JHU) for Novartis to determine the feasibility for future multicenter studies using MCC/CC as a primary endpoint.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypertonic Saline - 1 hour | Experimental | Drug: sodium chloride (7%)sodium chloride (7%); mucociliary clearance measured 1 hour post dose |
| Hypertonic Saline - 4 hours | Experimental | Drug: sodium chloride (7%)sodium chloride (7%); mucociliary clearance measured four hours post-dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Gender: Male or female (non-pregnant, non-lactating)
- Cystic fibrosis documented by a compatible clinical and radiographic presentation, and sweat chloride > 60 mEq/l or 2 disease causing CFTR mutations.
- Severity of Disease:
- Patient or legally authorized representative agrees to the patient/individual's participation in the study by signing and dating the informed consent form after the nature of the study has been fully explained and all questions have been satisfactorily answered.
Key exclusion criteria (6 listed)
- Unstable lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 >15% below recent (within 6 months) clinical measurements; or a significant new finding on chest radiograph (pneumothorax, lobar/segmental collapse) not considered a part of the usual, chronic progression of CF lung disease.
- Patients unable or unwilling to be withdrawn from hypertonic saline therapy, dornase alfa, or N-acetylcysteine 3 days prior to and for the duration of each Baseline and Treatment Period will be excluded.
- Patients unable to withhold use of long-acting bronchodilators (i.e., Salmeterol, Advair, Formoterol), anti-cholinergics, and vest therapy 12 hours prior to and for the duration of each treatment period.
- Patients unable to withhold short-acting bronchodilator 6 hours prior to and for the duration of each treatment period except as prescribed by the study protocol.
- Patients that have received an investigational drug or therapy during the preceding 30 days.
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 |
|---|---|---|
| sodium chloride (7%)Also: Hyper-Sal, Hypertonic saline (7%)4mL nebulized 7% sodium chloride | Drug | Hypertonic Saline - 1 hour, Hypertonic Saline - 4 hours |
Primary outcome
Change in Average Mucociliary Clearance (0-90 Minutes) at 1 and 4 Hrs Post Dose (MCC4hr - MCCbaseline; MCC1hr - MCCbaseline)
Time frame: 1-4 hours post-dose
Duration of action of hypertonic saline as determined by measurements of mucociliary clearance/cough clearance 4 hours post dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16421365Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006 Jan 19;354(3):241-50. doi: 10.1056/NEJMoa043891.
- Background: PubMed 16421364Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
- Background: PubMed 8665037Bennett WD, Olivier KN, Zeman KL, Hohneker KW, Boucher RC, Knowles MR. Effect of uridine 5'-triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1796-801. doi: 10.1164/ajrccm.153.6.8665037.
- Background: PubMed 17998363Donaldson SH, Boucher RC. Sodium channels and cystic fibrosis. Chest. 2007 Nov;132(5):1631-6. doi: 10.1378/chest.07-0288.
- Background: PubMed 10862159Pons G, Marchand MC, d'Athis P, Sauvage E, Foucard C, Chaumet-Riffaud P, Sautegeau A, Navarro J, Lenoir G. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol. 2000 Jul;30(1):25-31. doi: 10.1002/1099-0496(200007)30:13.0.co;2-c.
- Background: PubMed 12411282Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.
- Derived from this study: PubMed 37319354Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.
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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.
William Bennett, PhD principal investigator
University of North Carolina, Chapel Hill
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sodium chloride (7%) in people with Cystic Fibrosis, run by University of North Carolina, Chapel Hill at 2 sites 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 6 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 21 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 21 Aug 2012). 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?
Change in Average Mucociliary Clearance (0-90 Minutes) at 1 and 4 Hrs Post Dose (MCC4hr - MCCbaseline; MCC1hr - MCCbaseline) (time frame: 1-4 hours post-dose). 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 NCT01094704, which also lists 7 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 21 Aug 2012.