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Inflammatory Markers in Broncho-alveolar Lavage Fluid as Risk Factors for Lung Disease in Infants With Cystic Fibrosis: the I-BALL Study (I-BALL)

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ClinicalTrials.gov Identifier: NCT02907788
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : February 7, 2019
Sponsor:
Collaborators:
Emory University
UMC Utrecht
Information provided by (Responsible Party):
Dr. H.M. Janssens, Erasmus Medical Center

Brief Summary:
Airway disease, featuring intense inflammation, is the main cause of morbidity and mortality in cystic fibrosis (CF). Mechanisms of CF airway inflammation remain unclear, hampering development of better treatments.This time-sensitive ancillary study leverages a unique longitudinal cohort of CF infants, assessing the early phase of airway disease. Through the use of innovative cell and fluid based tools for in vivo profiling and in vitro testing of BALF samples, this translational effort will yield unprecedented insights into mechanisms of PMN dysfunction in CF, and assess new paths for early intervention.

Condition or disease
Cystic Fibrosis

Detailed Description:

Rationale: Airway disease, featuring early and intense inflammation and leading to progressive lung damage, is the main cause of morbidity and mortality in cystic fibrosis (CF). Mechanisms of CF airway inflammation remain unclear, hampering development of better treatments. Recent introduction of heel-prick screening for CF provides a unique longitudinal cohort of CF infants, in which the early phase of airway disease can be assessed. In our hospital the investigators set up a clinical protocol for monitoring these infants in a structured way, using chest computed tomography (CT) and bronchoscopies with collection of broncho-alveolar lavage fluid (BALF) to assess early lung damage. Our protocol is designed according to the protocol used by the Australian AREST-CF consortium. Preliminary data show that lipid profiles differ in BALF from CF infants with a high score for lung damage, compared with a low score (minimal lung damage). Some of these lipids are products of activated polymorphonuclear neutrophils (PMN's). Others are receptor-activating molecules involved in the resolution of inflammation and tissue injury. Also, in a pilot study, it was shown that CF airway PMNs are differently programmed than in normal airways, which leads to increased release of inflammatory factors and toxic enzymes. The hypothesize is that CFTR deficiency causes abnormal inflammatory signaling in the lung of CF infants, resulting in abnormal programming of infiltrating PMNs, and subsequently excessive and chronic lung disease.

Objectives: To better understand the progression of early CF lung disease the investigators aim to study lipid profiles and PMN dysfunction in relation to the severity of early lung disease in infants with CF, using BALF samples and peripheral blood. To optimally study these very precious samples, the investigators will make use of state-of-the-art technologies for in vivo profiling and in vitro testing of PMN function, including lipidomics and innovative cell- and fluid-based tools. Understanding the mechanisms at play in CF airway inflammation as it occurs in infants may lead to new paths for early intervention

Study design: Observational, exploratory in vitro study in BALF and peripheral blood from infants with CF, correlated with clinical data.

Study population: Children with CF diagnosed by heel-prick screening, who have a bronchoscopy and chest-CT for their annual check-up, at age 3 months (Utrecht),1, 3 or 5 years are eligible. Informed consent will be obtained from the parents.

Intervention: The bronchoscopy done to collect BALF is part of the routine clinical monitoring program. For this study, BALF that is not used for clinical testing will be used. Furthermore, venous puncture is performed for clinical routine blood tests, and one extra vial of EDTA blood will be drawn.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: Inflammatory Markers in Broncho-alveolar Lavage Fluid as Risk Factors for Lung Disease in Infants With Cystic Fibrosis: the I-BALL Study
Study Start Date : September 2014
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Group/Cohort
Cystic Fibrosis patients
Patient with cystic fibrosis diagnosed by Heel-prick screening
non-CF patients
Children who undergo bronchoscopy for another reason, without CF: eg gastro-esophageal reflux.



Primary Outcome Measures :
  1. Lipid profiles with early lung disease in CF. [ Time Frame: 5 years ]
    Lipidomics endpoints: The primary end-points are the different bioactive lipid levels in BALF of infants with CF using liquid chromatography (LC) coupled to Mass spectrometry (MS). Lipid profiles will be derived of the BALF supernatant

  2. Surface markers of reprogrammed PMNs in BALF of infants with CF [ Time Frame: 5 years ]
    Our primary endpoint for BALF cells flowcytometry analysis is surfacemarkers on airway PMNs (exocytosis of NE-rich granules), which was shown to correlate with lung function in chronic CF disease


Secondary Outcome Measures :
  1. PRAGMA-CT scores of infants with CF [ Time Frame: 5 years ]
    Secondary endpoints will include chest CT scores according to the PRAGMA scoring system


Biospecimen Retention:   Samples With DNA
  • Whole Blood
  • Bronchoscopies and bronchoalveolar lavage fluid (BALF)


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
All CF patients enrolled in the AREST-CF program of the paediatric CF centre at Sophia Children's Hospital and Wilhelmina Children's Hospital.
Criteria

Inclusion Criteria:

  • Diagnosed with CF, confirmed with 2 mutations found by genetic analysis, either from heel-prick screening or diagnosed later in life
  • Aged 3 months (Utrecht),1, 3 or 5 years, who undergo bronchoscopy and chest CT scan as part of the routine monitoring program for CF
  • Informed consent from parents

Exclusion Criteria:

  • Absence of previously given informed consent for use of encoded clinical data for scientific purposes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907788


Contacts
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Contact: Hettie M Janssens,, MD,PhD (+31) 10-7036679 h.janssens@erasmusmc.nl

Locations
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Netherlands
Erasmus MC -Sophia childrens hospital Recruiting
Rotterdam, Zuid Holland, Netherlands, 3015 CN
Contact: Hettie M Janssens, MD, PhD    (+31)-10-7036263    h.janssens@erasmusmc.nl   
Sponsors and Collaborators
Erasmus Medical Center
Emory University
UMC Utrecht
Investigators
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Principal Investigator: Rabindra Tirouvanziam, Assistant Professor Emory University

Additional Information:

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Responsible Party: Dr. H.M. Janssens, Dr, MD, PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02907788     History of Changes
Other Study ID Numbers: NL49725.078.14
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Dr. H.M. Janssens, Erasmus Medical Center:
Cystic fibrosis
Neutrophils
PMN
Inflammation
Lung disease
PRAGMA
Additional relevant MeSH terms:
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Cystic Fibrosis
Lung Diseases
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases