|- candidate number||10379|
|- NTR Number||NTR3078|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||22-sep-2011|
|- Secondary IDs||10-337 METC UMC Utrecht|
|- Public Title||Respiratory tract flora dynamics in infants with CF.|
|- Scientific Title||Dynamics of the respiratory tract flora in the first years of life: a comparative analysis between infants with cystic fibrosis and healthy controls.|
|- hypothesis||Our primary hypothesis is that the process of nasopharyngeal and fecal colonization from birth to childhood differs in quality and quantity between infants with CF and healthy controls and that these differences are related to subsequent respiratory morbidity in patients with CF. |
|- Healt Condition(s) or Problem(s) studied||Cystic Fibrosis (CF), Pathogens, Resistomics, microbiomics|
|- Inclusion criteria||1. Diagnosis of cystic fibrosis;|
2. Age < 3 months at time of inclusion.
|- Exclusion criteria||Other underlying disease or prematurity.|
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||7-mrt-2011|
|- planned closingdate||1-mrt-2014|
|- Target number of participants||80|
|- Interventions||In both groups of children (CF and healthy) transnasal nasopharyngeal swabs and saliva and feces samples will be collected.|
|- Primary outcome||We expect that in-depth knowledge about nasopharyngeal colonization profiles of newborns with CF and healthy controls will provide us with new and essential information for unravelling the pathogenic pathway by which upper respiratory bacteria might cause lower respiratory tract pathology in this patient group. In addition we feel that detailed studies of the development of resistance in pathogens in relation to evolution of the human resistome will help us in the future to design tailored antibiotic regimes to prevent resistance development in the respiratoiry pathogens. |
|- Secondary outcome||We will collect saliva samples to investigate the mucosal immune response in relation to natural boosting by pneumococcal colonization and childhood vaccinations in children with CF compared to controls.|
|- Timepoints||Visits and collection of respiratory, faecal and saliva specimens.|
Both groups will be seen monthly during the first 6 months of life (CF group first 3 months: weekly), every two months between the age of 6 months and 12 months and every 3 months between 12 months and 18 months to obtain a nasopharyngeal swab and a feces sample. Saliva will be obtained at the age of 3,6 and 12 months.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| S.M.P.J. Prevaes|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. C.K. Ent, van der|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU)|
(Source(s) of Monetary or Material Support)
|WKZ research Fund|
|- Brief summary||Background:|
The microbial flora of the upper respiratory tract forms a highly diversified ecological system, containing more than 400 bacterial species and intermittently hosting a wide range of different viruses, constantly interacting with each other and with the mucosal immune system. The balance of this complex ecological system is pivotal in preventing respiratory tract and systemic infections to occur. Microbial colonization of the upper respiratory tract starts soon after birth and gradually evolves in the first years of life; competitive microbial interactions and host factors determine the microbial profile in healthy infants. Infants with cystic fibrosis (CF) are often colonized with S. aureus and P. aeruginosa and are at increased risk for chronic pulmonary infections. Nasopharyngeal colonization profiles and changes in infants with CF in the first years of life are largely unknown, leaving possible windows of opportunity unnoticed. Insight and early interventions in the abnormal microbial competition and colonization in these patients might raise opportunities to prevent upper respiratory tract colonization and subsequent pulmonary disease. To gain more understanding about microbial colonization profiles, interactions, the impact of antibiotic use and respiratory viral infections and risks for subsequent pulmonary disease in children with CF, it is necessary to begin at the start and to unravel the microbial colonization profiles from a very early age. Modern high-throughput molecular techniques can facilitate detailed analysis of microbial profiles and -shifts, which was impossible until now using conventional culturing techniques.
Objective of the study:
We expect that in-depth knowledge about nasopharyngeal colonization profiles of newborns with CF and healthy controls will provide us with new and essential information for unravelling the pathogenic pathway by which upper respiratory bacteria might cause lower respiratory tract pathology in this patient group. In addition we feel that detailed studies of the development of risistance in pathogens in relation to evolution of the human resistome will help us in the future to design tailored antibiotic regimes to prevent resistance development in the respiratory pathogens.
We will collect saliva samples to investigate the mucosal immune response in relation to natural boosting by pneumococcal colonization and childhood vaccinations in children with CF compared to controls.
Study design and population:
This explorative prospective study aims to identify the sequential nasopharyngeal microbial colonization profile in the first 18 months of life of 20 newborns with CF (diagnosed with heelprick screening) and 60 age- and sex-matched healthy controls. Nasopharyngeal and fecal samples will be obtained regularly in all children. Saliva will be collected at the age of 3, 6 and 12 months. To identify differences and shifts in microbial flora, metagenomic analysis will be done high-throughput pyrosequencing. Conventional cultures and viral multiplex PCRs will be performed on monthly nasopharynx samples.
|- Main changes (audit trail)|
|- RECORD||22-sep-2011 - 18-okt-2011|