Cystic FibrosisNCT01155115
Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
A study testing Sputum Collection, Pulmonary Function Testing and Exhaled Nitric Oxide in people with Cystic Fibrosis and Primary Ciliary Dyskinesia, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
The objective of this study is to compare the lower airways inflammatory response to infection/pulmonary exacerbation among children known to have Primary Ciliary Dyskinesia (PCD) with children known to have Cystic Fibrosis (CF) as measured by the presence of inflammatory mediators in expectorated/induced sputum. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Cystic Fibrosis, Primary Ciliary Dyskinesia
- What is being tested?
- Sputum Collection, Pulmonary Function Testing and Exhaled Nitric Oxide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2010to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of Cystic Fibrosis (CF) as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease-causing mutations or a diagnosis of Primary Ciliary Dyskinesia (PCD) as follows: definite PCD (compatible phenotype, diagnostic abnormality of ciliary ultrastructure and/or two disease-causing gene mutations) or "probable" PCD (compatible phenotype, ciliary biopsy not diagnostic but low nasal NO (<100nl/min) with negative investigation screen for both CF and immunodeficiency
- Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
- 6-18 years of age at enrolment and able to perform reproducible spirometry
- Clinically stable at enrolment (FEV > 30%, oxyhaemoglobin sats > 93%)
- Ability to comply with study visits and study procedures
Who cannot join
- Respiratory culture positive for non-tuberculous mycobacteria (NTM), Stenotrophomonas maltophilia, Aspergillus fumigatus, Burkholderia cepacia complex, or Pseudomonas aeruginosa within past year.
- Use of intravenous antibiotics or oral quinolones within previous 14 days
- Use of inhaled antibiotics within the previous 28 days
- Pneumothorax or haemoptysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
The objective of this study is to compare the lower airways inflammatory response to infection/pulmonary exacerbation among children known to have Primary Ciliary Dyskinesia (PCD) with children known to have Cystic Fibrosis (CF) as measured by the presence of inflammatory mediators in expectorated/induced sputum.
Read the detailed description
The inflammatory response to infection and pulmonary exacerbation in CF is well documented, as is the response to intravenous antibiotic treatment. On the other hand, the inflammatory response to infection and treatment in PCD has not been well characterized. Given differences in disease progression, we hypothesize that children with CF respond to infection with a more exaggerated and prolonged inflammatory response than those with PCD.
- Conditions
- Cystic Fibrosis, Primary Ciliary Dyskinesia
- Being tested
- Sputum Collection, Pulmonary Function Testing, Exhaled Nitric Oxide
- Keywords
- pediatrics, CF, PCD, exacerbation, inflammatory markers, induced sputum
- Medical subject headings
- Cystic Fibrosis, Ciliary Motility Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sputum CollectionProcedure or surgery
Each study participant will be invited to expectorate sputum for culture, sensitivity, cytology and analysis of cytokine levels. Culture and sensitivity will be performed routinely at the beginning of a pulmonary exacerbation, as per standard of care, and will only be performed at subsequent visits if there is clinical indication. A volume of 5ml of sputum will be required at each visit for analysis. If the participant is unable to expectorate this volume of sputum, he/she will be invited to induce sputum instead as per standard protocols.
Pulmonary Function TestingProcedure or surgery
Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.
Exhaled Nitric OxideProcedure or surgery
The investigators will measure exhaled Nitric Oxide (eNO) at each visit according to the American Thoracic Society and European Respiratory Society guidelines using a chemiluminescence analyzer. Briefly, single breath exhalation are performed in triplicate at flows of 30, 50, 100, 150, 200 and 250 ml/s and eNO is measured at the end of the exhalation. The higher the flow rate the more peripheral the airways that are being sampled.
| Study group | Role | What they receive |
|---|---|---|
| Primary Ciliary Dyskinesia (PCD) Patients | Experimental | Not described Receives: Procedure: Sputum Collection; Procedure: Pulmonary Function Testing; Procedure: Exhaled Nitric Oxide |
| Cystic Fibrosis (CF) Patients | Experimental | Not described Receives: Procedure: Sputum Collection; Procedure: Pulmonary Function Testing; Procedure: Exhaled Nitric Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sputum bacterial colony count
For the following organisms (Staphylococcus aureus, Haemophilus influenza) in response to a prescribed treatment course of oral antibiotics.
Colony count will be done at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Measured: Up to 100 days
Airway Inflammatory Profile
As measured by sputum interleukin 8 (IL-8) at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).
Measured: Up to 100 days
Secondary outcomes (4)
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
Will be done at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Measured: Up to 100 days
Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients
Sputum will be collected at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).
Measured: Up to 100 days
Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.
FEV1 will be measured at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Measured: Up to 100 days
Other markers of airway inflammation
Measurement of sputum white cell and neutrophil count (absolute and relative values), neutrophil elastase, nitric oxide (NO), NO metabolites and arginase levels at three time points:
- during respiratory exacerbation (Visit 1 - Day 0),
- post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),
- and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).
Measured: Up to 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2010 (estimated)
- Study startJan 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 The Hospital for Sick ChildrenThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felix Ratjen, The Hospital for Sick Children
- Investigators
- Felix Ratjen, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01155115
- Sponsor's protocol ID
- 1000013966
- Status last verified
- May 2015
- First submitted
- 29 Jun 2010
- Last updated
- 22 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Grasemann H, McDonald N, Yuan XZ, Dell S, Waters V, Ratjen F. Lower Airway Nitrogen Oxide Levels in Children with Primary Ciliary Dyskinesia Is Linked to Neutrophilic Inflammation. J Pediatr. 2022 May;244:230-233. doi: 10.1016/j.jpeds.2022.01.040. Epub 2022 Feb 2.
PubMed 35120987Ratjen F, Waters V, Klingel M, McDonald N, Dell S, Leahy TR, Yau Y, Grasemann H. Changes in airway inflammation during pulmonary exacerbations in patients with cystic fibrosis and primary ciliary dyskinesia. Eur Respir J. 2016 Mar;47(3):829-36. doi: 10.1183/13993003.01390-2015. Epub 2015 Nov 19.
PubMed 26585432
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
- ClinicalTrials.gov ID
- NCT01155115
- Acronym / sponsor ID
- 1000013966
- Conditions
- Cystic Fibrosis, Primary Ciliary Dyskinesia
- Keywords
- pediatrics, CF, PCD, exacerbation, inflammatory markers, induced sputum
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to compare the lower airways inflammatory response to infection/pulmonary exacerbation among children known to have Primary Ciliary Dyskinesia (PCD) with children known to have Cystic Fibrosis (CF) as measured by the presence of inflammatory mediators in expectorated/induced sputum.
Detailed description
The inflammatory response to infection and pulmonary exacerbation in CF is well documented, as is the response to intravenous antibiotic treatment. On the other hand, the inflammatory response to infection and treatment in PCD has not been well characterized. Given differences in disease progression, we hypothesize that children with CF respond to infection with a more exaggerated and prolonged inflammatory response than those with PCD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary Ciliary Dyskinesia (PCD) Patients | Experimental | Procedure: Sputum Collection, Procedure: Pulmonary Function Testing, Procedure: Exhaled Nitric Oxide |
| Cystic Fibrosis (CF) Patients | Experimental | Procedure: Sputum Collection, Procedure: Pulmonary Function Testing, Procedure: Exhaled Nitric Oxide |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Diagnosis of Cystic Fibrosis (CF) as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease-causing mutations or a diagnosis of Primary Ciliary Dyskinesia (PCD) as follows: definite PCD (compatible phenotype, diagnostic abnormality of ciliary ultrastructure and/or two disease-causing gene mutations) or "probable" PCD (compatible phenotype, ciliary biopsy not diagnostic but low nasal NO (<100nl/min) with negative investigation screen for both CF and immunodeficiency
- Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
- 6-18 years of age at enrolment and able to perform reproducible spirometry
- Clinically stable at enrolment (FEV > 30%, oxyhaemoglobin sats > 93%)
- Ability to comply with study visits and study procedures
Key exclusion criteria (4 listed)
- Respiratory culture positive for non-tuberculous mycobacteria (NTM), Stenotrophomonas maltophilia, Aspergillus fumigatus, Burkholderia cepacia complex, or Pseudomonas aeruginosa within past year.
- Use of intravenous antibiotics or oral quinolones within previous 14 days
- Use of inhaled antibiotics within the previous 28 days
- Pneumothorax or haemoptysis
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 |
|---|---|---|
| Sputum CollectionEach study participant will be invited to expectorate sputum for culture, sensitivity, cytology and analysis of cytokine levels. Culture and sensitivity will be performed routinely at the beginning of a pulmonary exacerbation, as per standard of care, and will only be performed at subsequent visits if there is clinical indication. A volume of 5ml of sputum will be required at each visit for analysis. If the participant is unable to expectorate this volume of sputum, he/she will be invited to induce sputum instead as per standard protocols. | Procedure or surgery | Cystic Fibrosis (CF) Patients, Primary Ciliary Dyskinesia (PCD) Patients |
| Pulmonary Function TestingParticipants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines. | Procedure or surgery | Cystic Fibrosis (CF) Patients, Primary Ciliary Dyskinesia (PCD) Patients |
| Exhaled Nitric OxideThe investigators will measure exhaled Nitric Oxide (eNO) at each visit according to the American Thoracic Society and European Respiratory Society guidelines using a chemiluminescence analyzer. Briefly, single breath exhalation are performed in triplicate at flows of 30, 50, 100, 150, 200 and 250 ml/s and eNO is measured at the end of the exhalation. The higher the flow rate the more peripheral the airways that are being sampled. | Procedure or surgery | Cystic Fibrosis (CF) Patients, Primary Ciliary Dyskinesia (PCD) Patients |
Primary outcome
Change in sputum bacterial colony count
Time frame: Up to 100 days
For the following organisms (Staphylococcus aureus, Haemophilus influenza) in response to a prescribed treatment course of oral antibiotics. Colony count will be done at three time points: * during respiratory exacerbation (Visit 1 - Day 0), * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42), * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Airway Inflammatory Profile
Time frame: Up to 100 days
As measured by sputum interleukin 8 (IL-8) at three time points: * during respiratory exacerbation (Visit 1 - Day 0), * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42), * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).
4 secondary outcomes
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
Time frame: Up to 100 days
Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients
Time frame: Up to 100 days
Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.
Time frame: Up to 100 days
Other markers of airway inflammation
Time frame: Up to 100 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2015.
- Derived from this study: PubMed 35120987Grasemann H, McDonald N, Yuan XZ, Dell S, Waters V, Ratjen F. Lower Airway Nitrogen Oxide Levels in Children with Primary Ciliary Dyskinesia Is Linked to Neutrophilic Inflammation. J Pediatr. 2022 May;244:230-233. doi: 10.1016/j.jpeds.2022.01.040. Epub 2022 Feb 2.
- Derived from this study: PubMed 26585432Ratjen F, Waters V, Klingel M, McDonald N, Dell S, Leahy TR, Yau Y, Grasemann H. Changes in airway inflammation during pulmonary exacerbations in patients with cystic fibrosis and primary ciliary dyskinesia. Eur Respir J. 2016 Mar;47(3):829-36. doi: 10.1183/13993003.01390-2015. Epub 2015 Nov 19.
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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.
Felix Ratjen, MD principal investigator
The Hospital for Sick Children, Toronto Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sputum Collection, Pulmonary Function Testing and Exhaled Nitric Oxide in people with Cystic Fibrosis and Primary Ciliary Dyskinesia, run by The Hospital for Sick Children at 1 site in Canada.
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 5 inclusion and 4 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 22 May 2015. 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 Canada. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 sputum bacterial colony count (time frame: Up to 100 days). The study lists 2 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 NCT01155115, which also lists 2 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 22 May 2015.