|- candidate number||11266|
|- NTR Number||NTR3316|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||2-mrt-2012|
|- Secondary IDs||2011_082#B201152 METC AMC|
|- Public Title||Exhaled Markers in Asthma during Exacerbations.|
|- Scientific Title||Exhaled Markers in Asthma during exacerbations after inhaled corticosteroid withdrawal.|
|- hypothesis||We postulate that exhaled molecular profiling obtained from ‘breathprints’ by electronic nose:|
1. Is associated with the level of asthma control and;
2. Is associated with an inflammatory profile in induced sputum and blood in steroiddependent
controlled and uncontrolled phases of the disease.
|- Healt Condition(s) or Problem(s) studied||Asthma, Exacerbation|
|- Inclusion criteria||1. Age >18 years;|
2. Mild to moderately severe persistent asthma according to the criteria GINA :
A. Recurrent wheezing and/or chest tightness and/or shortness of breath AND;
B. Airway hyperresponsiveness, indicated by a positive methacholine or histamine
challenge with PC20 < 8 mg/ml anytime in the past 5 years OR;
C. 12% reversibility in FEV1 on salbutamol in the past 5 years.
3. Using at least a daily dose of inhaled corticosteroids (<= 500 ug ICS fluticasone or
4. Either allergic or non-allergic to a panel of common inhaled allergens;
5. Controlled asthma according to the criteria by GINA : All of the following:
A. Daytime symptoms less than twice/week;
B. No limitations of activities;
C. No nocturnal symptoms/awakening;
D. Need for reliever/rescue treatment less than twice/week;
E. PEF or FEV1 80% predicted;
F. No exacerbations in the past year.
6. OR Partly controlled asthma according to the criteria by the GINA : Any of the following
characteristics present in any week:
A. Daytime symptoms more than twice/week;
B. Limitations of activities;
C. Nocturnal symptoms/awakening;
D. Need for reliever/rescue treatment more than twice/week;
E. PEF or FEV1 < 80% predicted.
7. And exacerbations: one or more in the past 2 years. An exacerbation is defined as at
least one of three criteria :
A. Start of systemic corticosteroids, or increase from a stable maintenance dose for
at least 3 days;
B. Hospitalization or ER visit because of asthma, requiring systemic corticosteroids;
C. Deterioration of symptoms, lung function and/or rescue bronchodilators > 2 days
leading to ER or GP visit because of asthma, not requiring systemic
corticosteroids, but an increase/change in medication to prevent the exacerbation
from becoming severe.
8. Non-smoking or stopped smoking more than 12 months ago and a total maximum of 5
9. No other clinically significant abnormality on history and clinical examination;
10. Able to give written and dated informed consent prior to any study-specific procedures.
|- Exclusion criteria||1. Change in the dose of ICS within 4 weeks prior to screening;|
2. A course of oral corticosteroids, antibiotics or a respiratory infection within 4 weeks prior
to the study;
3. Use of ipratropium, anti-IgE or oral corticosteroids;
5. Concomitant disease or condition which could interfere with the conduct of the study, or
which treatment might interfere with the conduct of the study, or which would, in the
opinion of the investigator, pose an unacceptable risk to the patient in this study;
6. Unwillingness or inability to comply with the study protocol for any other reason.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||6-mrt-2012|
|- planned closingdate||31-dec-2012|
|- Target number of participants||30|
|- Interventions||Cessation of inhaled steroids during 8 weeks.|
|- Primary outcome||Breathprints of volatile organic compounds which are associated with loss of asthma control (deterioration in symptoms and lung function) after interruption of inhaled steroid therapy.|
|- Secondary outcome||1. The critical VOCs of these breathprints in exhaled air by gas chromatography
and mass spectrometry (GC-MS);|
2. The individual biomarkers in sputum, blood and EBC that are associated with
asthma control and electronic nose and GC-MS breathprints;
3. The effect of loss of asthma control by interruption of inhaled steroids on
4. The association between markers of coagulation, inflammation and exhaled molecular profiles assessed by electronic nose and GC-MS.
|- Timepoints||Visit 1: Screening at week -12 to -2;|
Visit 2: Baseline at week 0;
Visit 3: Exhaled breath at week 4;
Visit 4: Exacerbation at week X or 8;
Visit 5: Remission at week X+4 or 12.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. Niki Fens|
|- CONTACT for SCIENTIFIC QUERIES||Dr. Niki Fens|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale:|
In asthma, symptoms and lung function are only moderately associated with a change in
airways inflammation, as in a period of loss of control or exacerbation. Therefore, there is a
need for biomarkers that reflect inflammation more directly and that are easy to obtain. Direct
on-line assessment of exhaled air volatile organic compounds (VOCs) may avoid the need of
special tests in expert centres and will particularly be suitable in primary care and for the socalled
poor-perceivers of exacerbation symptoms.
The current study will assess the ability of exhaled breath molecular profiling using an
electronic nose and gas chromatography and mass spectrometry to discriminate breath
molecular profiles (breathprints) from asthma patients during controlled and uncontrolled
periods. For this purpose, an exacerbation will be induced by interruption of inhaled
We postulate that exhaled breathprints as measured by electronic nose:
1. Are associated with the level of asthma control and;
2. Are associated with an inflammatory profile in induced sputum and blood in steroiddependent
controlled and uncontrolled phases of the disease.
1. To identify breathprints of volatile organic compounds which are associated with loss of
asthma control (deterioration in symptoms and lung function) after interruption of inhaled
2. To examine the critical VOCs of these breathprints in exhaled air by gas chromatography
and mass spectrometry (GC-MS).
3. To identify individual biomarkers in sputum, blood and EBC that are associated with
asthma control and electronic nose and GC-MS breathprints.
4. To examine the effect of loss of asthma control by interruption of inhaled steroids on
5. To examine whether there is an association between markers of coagulation,
inflammation and exhaled molecular profiles assessed by electronic nose and GC-MS.
14 weeks prospective follow-up study. Reduction of clinical control and reestablishment
of control will be obtained by cessation and restoration of inhaled steroids.
30 patients with mild to severe persistent asthma using inhaled
Breath measurements by electronic nose platform and GC-MS and sputum
and blood biomarkers will be monitored at baseline, and during withdrawal and restoration of
Main study parameters/endpoints:
Change in eNose breathprint at loss of control
compared to stable condition, after completion of 8 weeks steroid withdrawal phase.
Nature and extent of the burden and risks associated with participation, benefit and
Patients will interrupt regular inhaled corticosteroids. This will cause a
transient loss of asthma control. The model that is used in this study proved to be safe.
|- Main changes (audit trail)|
|- RECORD||2-mrt-2012 - 24-mei-2012|