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

May 21, 2015 updated by: Felix Ratjen, The Hospital for Sick Children

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 100 days
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)).
Up to 100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
Time Frame: Up to 100 days

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.
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

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)).
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

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.
Up to 100 days
Other markers of airway inflammation
Time Frame: Up to 100 days

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)).
Up to 100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Hospital for Sick Children

Investigators

  • Principal Investigator: Felix Ratjen, MD, The Hospital for Sick Children, Toronto Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

June 29, 2010

First Submitted That Met QC Criteria

June 29, 2010

First Posted (Estimate)

July 1, 2010

Study Record Updates

Last Update Posted (Estimate)

May 22, 2015

Last Update Submitted That Met QC Criteria

May 21, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1000013966

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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