Using nitrogen-washout to detect lung disease after donor-stem cell transplantation
| ISRCTN | ISRCTN13301994 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13301994 |
| Secondary identifying numbers | EKNZ 340/13 |
- Submission date
- 27/09/2018
- Registration date
- 29/11/2018
- Last edited
- 16/12/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Bronchiolitis obliterans (BO) and its clinical equivalent, bronchiolitis obliterans syndrome (BOS), is a severe lung complication in patients who have received a stem cell transplantation. It has many complications and a high rate of death. BO affects the small airways in the lung and is defined as the development of a new fixed airways obstruction. The obstruction usually occurs within the first two years after stem cell-transplantation but may develop as late as 5 years later. Current estimates suggest that about 2% - 5% of all patients who have received donor stem cell transplantation, and about 14% of patients in whom the body rejects the donated stem cells, are affected. Unfortunately, the survival and treatment of BOS over the last 20 years has not improved, with an overall survival of about 15% at 5 years. Patients present with dyspnoea (breathlessness) by exertion, dry cough, wheezing and dry crackles on lung auscultation (stethoscope). However, in early disease, patients may have no respiratory symptoms and lung function tests could be normal, before the criteria for BOS are met. Symptoms and signs of airflow obstruction on spirometry (lung test) do not occur until the disease of the small airways is widespread and lesions are more likely to be irreversible. The gold standard for diagnosing BOS still requires transbronchial, thoracoscopic or open lung biopsy (tissue sample), which are all invasive methods and several studies have noted mortality rates of 30% to 60%. Therefore, more sensitive and reproducable measurements are needed to detect the disease earlier. The aim of this study is to find out whether a test called nitrogen (N2)-washout can be used for the early detection of BO after stem cell transplantation.
Who can participate?
Patients aged 18 and older undergoing stem cell transplantation
What does the study involve?
All participants undergo lung function tests and complete a questionnaire on breathing symptoms and medication. All the measurements take about 40-50 minutes per patient and are carried out once before transplantation, monthly for the first year after transplantation, and every three months in the second year after transplantation.
What are the possible benefits and risks of participating?
The possible benefit of the study outweighs the risks in that an earlier identification of BO may lead to improved clinical outcomes. Lung function tests may lead to coughing, dizziness or acute hyperventilation (fast breathing) caused by repeated deep expirations and inspirations (breathing out and in). These are temporary in nature.
Where is the study run from?
University Hospital Basel (Switzerland)
When is the study starting and how long is it expected to run for?
December 2015 to December 2020
Who is funding the study?
University Hospital Basel (Switzerland)
Who is the main contact?
Dr Desiree Schumann
Contact information
Public
University Hospital Basel
Petersgraben 4
Basel
4051
Switzerland
Study information
| Study design | Single-center longitudinal observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Scientific title | The use of N2-washout for the early detection of bronchiolitis obliterans after allogenic stem cell transplantation |
| Study acronym | Adorable Study |
| Study objectives | The trialists hypothesise that an abnormal phase III-slope (SBW) or an increased LCI (MBW) in patients with stable lung function after hematopoietic stem cell transplantation, can detect early changes in small airways (i.e. bronchiolitis obliterans) before clinical symptoms occur. |
| Ethics approval(s) | Ethikkommission Nordwest und Zentralschweiz, 26/09/2014, ref: EKNZ 340/13 |
| Health condition(s) or problem(s) studied | Bronchiolitis obliterans in allogenic stem cell transplantation patients |
| Intervention | All measurement methods, principally N2-MBW, DTG-SBW and, depending on the clinical picture, FeNO, DLCO, FOT, spirometry and body plethysmography, will be carried out by the researchers in accordance with international guidelines once before transplantation, monthly for the first year after transplantation and every three months in the second year after transplantation. A validated measurement system will be used for the washout measurements and the evaluation will be performed in accordance with the recommended standard. For this, either the measuring systems’ software (Eco Medics AG) or an external software, Lungsim im Matlab R 2006a (The MathWorks, Inc, Version 7.2), will be used. The latter was specifically developed for the advanced offline analysis of washout measurements. Changes in LCI, Scon and Sacin, microbiological parameters such as colonization, infection and dysbiosis, and serum biomarkers of inflammation or extracellular matrix turnover such as collagen formation and degradation molecules, are measured over time following allogenic stem cell transplantation in: 1. Patients without pulmonary symptoms and low or high GvHD risk according to the GvHD risk score 2. Patients with pulmonary symptoms and lung function criteria for bronchiolitis obliterans 3. Patients with pulmonary symptoms, lung function criteria for BO and histological confirmation of either lymphoproliferative or constrictive BO |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Lung clearance index (LCI) is measured with the multiple breath washout technique (N2-MBW) before transplantation, monthly for the first year after transplantation and every three months in the second year after transplantation |
| Secondary outcome measures | Measured before transplantation, monthly for the first year after transplantation and every three months in the second year after transplantation: 1. Scon and Sacin are measured using single-breath washout measurements 2. Microbiological parameters such as colonization, infection and dysbiosis, measured using oropharyngeal swabs 3. Serum biomarkers of inflammation or extracellular matrix turnover such as collagen formation and degradation molecules, measured using blood samples |
| Overall study start date | 01/12/2015 |
| Completion date | 31/12/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 200 |
| Total final enrolment | 181 |
| Key inclusion criteria | 1. 18 years and older 2. Patients undergoing allogenic stem cell transplantation |
| Key exclusion criteria | 1. Failure to provide informed consent 2. Patients too ill or unfit to undergo a lung function test 3. Patients who have undergone stem cell transplantation before inclusion |
| Date of first enrolment | 01/01/2016 |
| Date of final enrolment | 31/12/2018 |
Locations
Countries of recruitment
- Switzerland
Study participating centre
Petersgraben 4
Basel
4051
Switzerland
Sponsor information
Hospital/treatment centre
Petersgraben 4
Basel
4051
Switzerland
"ROR" |
https://ror.org/04k51q396 |
|---|
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The trialists strive to publish all data at conferences and/or in peer-reviewed journals. Additional documents will be available on request. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
16/12/2020: Total final enrolment added.
