Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

This study is currently recruiting participants.
Verified August 2013 by The Hospital for Sick Children
Sponsor:
Information provided by (Responsible Party):
Felix Ratjen, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01155115
First received: June 29, 2010
Last updated: August 30, 2013
Last verified: August 2013

June 29, 2010
August 30, 2013
January 2010
January 2014   (final data collection date for primary outcome measure)
  • Change in sputum bacterial colony count [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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)).
Same as current
Complete list of historical versions of study NCT01155115 on ClinicalTrials.gov Archive Site
  • Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]

    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.
  • 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 ] [ Designated as safety issue: Yes ]

    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)).
  • 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 ] [ Designated as safety issue: No ]

    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.
  • Other markers of airway inflammation [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]

    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)).
Same as current
Not Provided
Not Provided
 
Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cystic Fibrosis
  • Primary Ciliary Dyskinesia
  • Procedure: Sputum Collection
    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.
  • Procedure: Pulmonary Function Testing
    Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.
  • Procedure: Exhaled Nitric Oxide
    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.
  • Experimental: Primary Ciliary Dyskinesia (PCD) Patients
    Interventions:
    • Procedure: Sputum Collection
    • Procedure: Pulmonary Function Testing
    • Procedure: Exhaled Nitric Oxide
  • Experimental: Cystic Fibrosis (CF) Patients
    Interventions:
    • Procedure: Sputum Collection
    • Procedure: Pulmonary Function Testing
    • Procedure: Exhaled Nitric Oxide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
52
April 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Both
6 Years to 18 Years
No
Contact: Felix Ratjen, MD 416-813-6167 felix.ratjen@sickkids.ca
Canada
 
NCT01155115
1000013966
Yes
Felix Ratjen, The Hospital for Sick Children
The Hospital for Sick Children
Not Provided
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto Canada
The Hospital for Sick Children
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP