Kinetics of YKL-40 Protein in Serum of Cystic Fibrosis Patients (Kin_YKL_CF)

Chitinase and Cystic Fibrosis Disease Evolution

YKL-40 is proposed as a biomarker of various inflammatory disease diabetes and lung disease including cystic fibrosis. In those cross-sectional studies, a unique value of YKL-40 is used to correlate with clinical, physiological, or biological determinants of disease severity (like FEV1 for example in lung disease). There is only one longitudinal study that showed a correlation between circulating levels of YKL-40 and the decline of lung function in smokers sampled from the general population. In order to better understand the potential role of YKL-40 in CF pathophysiology, and to determine its potential role as a biomarker of disease evolution, it is essential to proceed with further clinical evaluation. The investigators propose to perform an observational prospective cohort study to determine if variation of YKL-40 concentration over 24 months correlates with the clinical evolution of the patients.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

Detailed Description

Observational prospective cohort: The primary objective of the study is to determine if variation of YKL-40 concentration (in blood or sputum) over 24 months will correlate with the biological or clinical condition of the patients. For this study, only patients (FEV1 > 30%) positive for Pseudomonas in the past year will be included, while B Cepacia positive patients will be excluded. There are presently 200 patients meeting these inclusion criteria. The investigators choose to limit the study population to patients with Pseudomonas since they are more likely to have FEV1 changes or clinical evolution during the observation period. The investigators expect a high participation rate since the only obligation for the patients is to provide samples at each visit. A blood (for serum and DNA) and sputum samples will be taken at each regular clinic visit (3-4/year-no evidence of exacerbation in the past two weeks) as well as at the beginning and at the end of an exacerbation treated with IV antibiotics. This will also allow the investigators to determine if there is a change in YKL-40 during an exacerbation. The patients will be followed for a period of 24 months. In parallel to the measurement of YKL-40 in blood and airway secretions, other biological parameters will be monitored (see list below) as well as the BMI, lung function (FEV1/FVC), oxygen saturation and heart rate. The investigators will also monitor the glucose metabolism status of the patient (IGT, CFRD) and the number of exacerbations per year as well as any significant changes in the microbiology status of the patients. A pulmonary exacerbation will be defined as an acute exacerbation of pulmonary symptoms that in the opinion of the CF physician is severe enough to require intravenous antibiotics. The proposed sample size, was shown by power calculation, to be sufficient to demonstrate a meaningful changes in YKL-40 (initial-final) given plausible values of the standard deviation of this difference between patients.

• Study Type: Observational
• Enrollment (Actual): 188

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2W 1R7
      • CRIMontreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will follow the patients (<18-year-old) for a period of 24 months. In parallel to the measurement of YKL-40 in blood and airway secretions we will monitor other biological parameters (see list below) as well as the BMI, lung function (FEV1/FVC), oxygen saturation and heart rate. We will monitor the glucose metabolism status of the patient (IGT, CFRD) and the number of exacerbations per year as well any significant changes in the microbiology status of the patients. A pulmonary exacerbation will be defined as an acute exacerbation of pulmonary symptoms that in the opinion of the CF physician is severe enough to require intravenous antibiotics.

Description

Inclusion Criteria:

1. man and woman ≥ 18 ans.
2. documented CF diagnostic (sweat test or genotype).
3. FEV1 ≥ 25%
4. Stable: no infection in the last two weeks before the visit.

Exclusion Criteria:

1. Exacerbation with respiratory symptoms with ou without hospitalization in the last two weeks 2. Exacerbation treated with IV antibiotics. 3. Patients with B. Cepacia

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Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood concentration of YKL-40 (ng/ml)	Trajectory of YKL-40 over time	at every outpatient regular visit over a period of 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Blood concentration of YKL-40 (ng/ml) during an exacerbation	Variation of YKL-40 during exacerbation	At the beginning and at the end of an exacerbation during the 24 months of follow-up

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Investigators: Principal Investigator: Yves Berthiaume, Md, Institut de recherches cliniques de Montreal

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: November 11, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: inflammation; Cystic fibrosis; cytokine; Pulmonary exacerbation; Chitinase; Cystic fibrosis related diabetes
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: Kin_YKL-40_CF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not possible since the consent form did not include the possibility to share data with other investigators.