We aim to evaluate the changes in the composition and the function of the respiratory microbiome after the initiation of targeted CFTR therapy. Second we want to relate the change in respiratory biochemical and microbial environment to clinical…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Bacterial sequences in sputum, broncho-alveolar lavage fluid and oral and
nasal wash.
* Metabolic profiles in broncho-alveolar lavage fluid and oral wash by mass
spectrometry.
* Volatile metabolites in breath.
Secondary outcome
* Bacterial culture result from sputum and broncho-alveolar lavage fluid.
* Lung function test results (FEV1/FVC, etc).
* Routine plasma parameters of (chronic) inflammation (IgG, CRP, leukocyte
count) and inflammatory profiles of sputum and broncho-alveolar lavage fluid
measured by luminex.
* Quality of life and fatigue assessments.
Background summary
The lungs of patients with CF are characterized by (1) impaired mucus
clearance, (2) acidic milieu, (3) increased neutrophils but impaired function
and (4) increased bacterial loads. Novel therapies target the CF transport
receptor (CFTR) and increase it*s activity. They improve lung function in
patients with a specific mutation. However, very little is known about the
influence of the targeted CFTR therapies on the respiratory microbiome. One of
the major challenges in CF is to limit the colonization of the respiratory
tract by well-adapted microbes such as Pseudomonas and maintain a healthy
respiratory flora.
Study objective
We aim to evaluate the changes in the composition and the function of the
respiratory microbiome after the initiation of targeted CFTR therapy. Second we
want to relate the change in respiratory biochemical and microbial environment
to clinical changes (for example lung function). Finally, we will explore the
differences in pre-medication respiratory microbiome / metabolome between
patients that clinically respond and do not respond to treatment.
Study design
Longitudinal observational cohort study.
Study burden and risks
All assessment will be performed in conjunction with routine visits to the
outpatient clinic as much as possible. The most important additional procedure
for the patient are two additional bronchoscopies in a selected group of
patients. This procedure is unpleasant but is of low risk in the patients that
are included for bronchoscopy. The patient will not have benefit from
participation in the study. We aim for improved treatment of bacterial
dysbalance in the respiratory tract of all patients with CF and in that respect
the results of the study may improve treatment in the future for the patients
participating in the study or any patient with similar characteristics.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Patients with a (predominant) class II mutation (almost exclusively homozygous Phe508del) for cystic fibrosis (N<=20) who will be started on Ivacaftor/Lumacaftor (CFTR targeted therapy; Orkambi) therapy will be included in this longitudinal observational study.
Exclusion criteria
For the bronchoscopy (part of the research protocol) the following patients will be excluded:
* Pre-lung transplant trajectory
* No informed consent for the procedure
* Deemed inappropriate by the treating physician.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL60220.018.16 |