Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02907788 |
Other study ID # |
NL49725.078.14 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
September 2014 |
Est. completion date |
January 2021 |
Study information
Verified date |
November 2021 |
Source |
Erasmus Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical Trial 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.
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.