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

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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.


Condition Intervention
Cystic Fibrosis
Primary Ciliary Dyskinesia
Procedure: Sputum Collection
Procedure: Pulmonary Function Testing
Procedure: Exhaled Nitric Oxide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • 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)).


Secondary Outcome Measures:
  • 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)).


Estimated Enrollment: 52
Study Start Date: January 2010
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primary Ciliary Dyskinesia (PCD) Patients 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: Cystic Fibrosis (CF) Patients 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.

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.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01155115

Contacts
Contact: Felix Ratjen, MD 416-813-6167 felix.ratjen@sickkids.ca

Locations
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Felix Ratjen, MD    416 813 6167    felix.ratjen@sickkids.ca   
Principal Investigator: Felix Ratjen, MD         
Sub-Investigator: Timothy Leahy, MB         
Sub-Investigator: Valerie Waters, MD         
Sub-Investigator: Yvonne Yau, MD         
Sub-Investigator: Sharon Dell, MD         
Sub-Investigator: Hartmut Grasemann, MD         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto Canada
  More Information

No publications provided

Responsible Party: Felix Ratjen, Division Head, Respiratory Medicine, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01155115     History of Changes
Other Study ID Numbers: 1000013966
Study First Received: June 29, 2010
Last Updated: August 30, 2013
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
pediatrics
CF
PCD
exacerbation
inflammatory markers
induced sputum

Additional relevant MeSH terms:
Ciliary Motility Disorders
Kartagener Syndrome
Cystic Fibrosis
Dyskinesias
Fibrosis
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Bronchiectasis
Bronchial Diseases
Respiratory System Abnormalities
Dextrocardia
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Situs Inversus
Genetic Diseases, Inborn
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Infant, Newborn, Diseases
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes
Nitric Oxide
Bronchodilator Agents

ClinicalTrials.gov processed this record on August 28, 2014