In this study we aim to use minimally invasive real-time techniques including OCT, HHGM, eNose and/or GC-MS for the evaluation of the effect of BT and determine response predictors. To evaluate innovative diagnostic techniques that might be able to…
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Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To obtain visual qualitative remodeling characteristics and quantitative
measurements of OCT airway images and their 3-D reconstructions before and
after BT and the non-treated ML.
- To obtain visual qualitative remodeling characteristics and quantitative
measurements of ex-vivo HHGM images obtained from airway wall biopsies before
and after BT and the non-treated ML.
- To identify and quantify ASM, ECM and inflammatory components in OCT images.
- To identify and quantify ASM, ECM and inflammatory components in HHGM images.
- To correlate OCT and HHGM images with histology results.
- To correlate OCT and HHGM images to clinical outcomes including responders /
non - responders analysis
- To identify and quantify changes in VOCs by eNose and/or GC-MS before and
after BT and correlate this to omics approaches in blood (and brushes if
available) .
Secondary outcome
- To validate the ASM measurements by OCT in a larger number of patients, as
has been done before in our previous work.
- To validate the distinctive patterns we have found in exhaled VOCs in
responders and non-responders to BT with GC-MS in a larger number of patients.
- To phenotype severe asthma and perform clinical outcome analyses that
includes induced sputum, bronchial hyper-responsiveness (BHR, PC20
methacholine), forced expiratory volume in 1 second (FEV1) and fractional
exhaled nitric oxide (FeNO) and molecular parameters including RNA-derived
transcriptomes extracted from brushes.
- To evaluate the sub-acute effects of BT from the collected data at the last
BT bronchoscopy 6 weeks after the first treatment procedure (BT1).
- To detect and evaluate the changes from measurements in the brushes and
Bronchoalveolar lavage fluid (BALF) before and after therapy
- To detect and evaluate the differences from measurements in the brushes and
BALF between the responders and non-responders.
- To evaluate the sub-acute effect of BT by analysing the biopsies, OCT
measurements and HHGM images 6 weeks after treatment.
Background summary
Bronchial thermoplasty (BT) is a novel endobronchial treatment for severe
asthma. The treatment is based on selective heating of the airways which aims
to attenuate the airway smooth muscle (ASM) and airway remodeling. The
reduction in ASM mass and changes in the structure of the airways have been
shown in several histological studies. To assess and evaluate the ASM or other
airway wall components like the extra cellular matrix (ECM), histological
staining is the current gold standard. In the past years, less invasive and
even more accurate techniques have been developed as diagnostic tools. At
first, optical coherence tomography (OCT) is a minimal bronchoscopic invasive
technique which generates high resolution, real-time cross sectional images of
the airway wall. Secondly, higher harmonic generation microscopy (HHGM) is a
relative new technique which enables assessment of the ECM components in airway
wall biopsies in several minutes of time without fixation and staining.
Thirdly, breathomics, which is analysis of volatile organic compounds (VOC*s)
in exhaled breath, has great potential as a non-invasive test to monitor
inflammation in the lungs. This can be done by using either an electronic nose
(eNose) or gas chromatography-mass spectrometry (GC-MS).
Study objective
In this study we aim to use minimally invasive real-time techniques including
OCT, HHGM, eNose and/or GC-MS for the evaluation of the effect of BT and
determine response predictors. To evaluate innovative diagnostic techniques
that might be able to monitor changes in the airways in severe asthma patients
treated with BT, and to obtain more insight in the working mechanism and
responder profile of BT.
Study design
This is an investigator-initiated, observational study where different
monitoring techniques are evaluated (OCT, HHGM, and eNose and/or GC-MS) in
comparison with histology and clinical parameters including asthma
questionnaires and quality of life scores.
Study burden and risks
This study has a two-fold purpose; first to further unravel the working
mechanism of BT in severe asthma and secondly gather more insight for a better
patient selection. These objectives can only be achieved by linking
patient-reported outcomes to airway structure/function, which is the principal
aim of the study proposed.
The patient benefit of study participation is that he/she is offered a severe
asthma treatment that is proven effective and safe long-lasting benefit but
unfortunately not yet reimbursed in the Netherlands yet. Moreover, we are the
only center which offer this treatment.
For study purposes we ask patients to undergo one extra bronchoscopy. This
bronchoscopy is on top of a single standard screening bronchoscopy before BT
and the bronchoscopy procedures for treatment. Before and after therapy airway
sampling and OCT imaging is performed along with standard of care procedures
such as sputum induction, pulmonary function tests and questionnaires. The
bronchoscopies will be performed under deep sedation (midazolam and/or
propofol) to minimize patient discomfort. Previous experiences in research
bronchoscopies in severe asthma patients by our group and others have proven
these procedures to be safe. To our opinion the burden one additional
bronchoscopy is justified by the scientific insights that can be obtained in
this important study in which a novel severe asthma treatment is offered that
is otherwise not available.
For the OCT measurements we expect sedation time in the endoscopy suite to be
prolonged by 8 minutes. Based on our experiences with OCT in previous AMC
initiated trials, and literature where OCT measurements of the airway wall are
obtained, we state that imaging by OCT is safe and poses no risk for the
patient. Images made by HHGM are ex-vivo and thereby are of no burden or risk
to the patients. Another extra additional procedure in this study is the
exhaled breath sampling, which is a non-invasive procedure, therefore the risks
of this procedure are negligible.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Patient is an adult, aged 18 years or older, and is scheduled to undergo
(re-)BT treatment according to the Alair System directions for use, according
to the BT registry protocol.
2. Patient is able to read, understand, and sign a written IC to participate in
this study and able to comply with the registry requirements.
3. Patient meets the inclusion criteria of the BT registry
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Use of investigative drugs or intervention trials in the 4 months prior to
enrolment or during the duration of the study.
2. Any condition or compliance issue which in the opinion of the investigator
might interfere with participation in the study.
3. Any exclusion criteria from the BT-registry
Design
Recruitment
Medical products/devices used
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 | NL80306.018.22 |