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

Cystic Fibrosis Clinical Trial

Official title:

Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01155115
• Other study ID #: 1000013966
• Status: Completed
• Phase: N/A
• First received: June 29, 2010
• Last updated: May 21, 2015
• Start date: January 2010
• Est. completion date: December 2014

Study information

• Verified date: May 2015
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ciliary Motility Disorders
• Cystic Fibrosis
• Dyskinesias
• Fibrosis
• Kartagener Syndrome
• Primary Ciliary Dyskinesia

Intervention

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.
• Pulmonary Function Testing
Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.
• 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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 100 days	No
Primary	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)).	Up to 100 days	No
Secondary	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.	Up to 100 days	No
Secondary	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)).	Up to 100 days	Yes
Secondary	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.	Up to 100 days	No
Secondary	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)).	Up to 100 days	No