- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02907788
Inflammatory Markers in Broncho-alveolar Lavage Fluid as Risk Factors for Lung Disease in Infants With Cystic Fibrosis: the I-BALL Study (I-BALL)
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Zuid Holland
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Rotterdam, Zuid Holland, Netherlands, 3015 CN
- Erasmus MC -Sophia childrens hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Cystic Fibrosis patients
Patient with cystic fibrosis diagnosed by Heel-prick screening
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non-CF patients
Children who undergo bronchoscopy for another reason, without CF: eg gastro-esophageal reflux.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lipid profiles with early lung disease in CF.
Time Frame: 5 years
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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
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5 years
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Surface markers of reprogrammed PMNs in BALF of infants with CF
Time Frame: 5 years
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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
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5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PRAGMA-CT scores of infants with CF
Time Frame: 5 years
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Secondary endpoints will include chest CT scores according to the PRAGMA scoring system
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5 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rabindra Tirouvanziam, Assistant Professor, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL49725.078.14
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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