Study of Pulmonary MRI for the Diagnosis of Bronchiolitis Obliterans Syndrome After Allogeneic Stem Cell Transplantation (IRM-A)
Primary Purpose
Bronchiolitis Obliterans
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
lung MRI
Sponsored by
About this trial
This is an interventional diagnostic trial for Bronchiolitis Obliterans focused on measuring lung MRI performance, UTE, quantification, oxygen transfer, Bronchiolitis Obliterans syndrome, allogeneic stem cell transplantation
Eligibility Criteria
Inclusion Criteria:
- Patient ≥ 18 yo ;
- Patient who underwent an allogeneic stem cell transplantation (SCT)
- > 3 months post-SCT
With evidence of
- respiratory symptoms, and/or
- Pathological PFTs defined by : obstructive syndrome (FEV1 :vital capacity/CVF < 0.7), FEV1 < 0.75 of pre-SCT values, residual volume > 120%, and/or ;
- Altered PFTs consistent with 0p stage described in lung transplantation BOS: FEV1 decline ≥ 10 % and/or FEF25-75 decline ≥ 25% compared to pre-SCT PFTs, and/or ;
- Abnormal chest CT-scan with findings consistent with BOS: evidence of air trapping on expiratory CT-scan, bronchiectasis, and/or airway thickening.
Exclusion Criteria:
- Contraindication for MRI ;
- Contraindication of oxygen administration ;
- Decompensation of altered respiratory function ;
- Acute respiratory infection (bacterial, fungal or viral) documented in the last 6 weeks ;
Sites / Locations
- CHU BordeauxRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lung MRI
Arm Description
lung MRI concordance as compared to chest CT-scan for the description of morphological abnormalities necessary for the diagnosis of BOS after HSCT. It will be evaluated using lung MRI performed after inclusion (D0) using a standardized procedure
Outcomes
Primary Outcome Measures
lung MRI concordance as compared to chest CT-scan
lung MRI concordance as compared to chest CT-scan for the description of morphological abnormalities necessary for the diagnosis of BOS after HSCT. It will be evaluated using lung MRI performed after inclusion (Baseline) using a standardized procedure. The agreement between MRI and chest CT-scan for the presence or absence of the following features, will be measured at the segmental level: airway thickening, bronchiectasis, air trapping.
Secondary Outcome Measures
Bhalla Score precision in morphological MRI
Measure of Bhalla Score precision in morphological MRI for the diagnosis of post-transplant BOS
Bhalla Score in CT scan
Bhalla Score in CT scan
oxygen transfer capacity
Measure of oxygen transfer capacity (percentage of intra-pulmonary signal variation before and after inhalation of oxygen);
Force Expiratory Volume
Force Expiratory Volume (FEV, l)
FEV1/VC
FEV1/VC (Tiffeneau),
Residual volume
Residual volume (l)
total lung capacity
Total lung capacity (l)
BOS stages
BOS stages (0 : FEV1 > 90%, and FEF25-75 > 75% from baseline; 0p : 10-19% decrease in FEV1, and/or by a >/= 25% decrease in FEF 25-75 from baseline; 1: FEV1 60-79% ; 2: FEV1 40-59% ; 3: FEV1</= 39)
intra-observer repeatability of the Bhalla score in CT scan
Intraclass coefficient and Bland-Altman's test
intra-observer repeatability of the Bhalla score in MRI
Intraclass coefficient and Bland-Altman's test
intra-observer repeatability of the measure of oxygen transfer capacity
Intraclass coefficient and Bland-Altman's test
inter-observer reproducibility of the Bhalla score in CT scan
Intraclass coefficient and Bland-Altman's test
inter-observer reproducibility of the Bhalla score in MRI
Intraclass coefficient and Bland-Altman's test
inter-observer reproducibility of the measure of oxygen transfer capacity
Intraclass coefficient and Bland-Altman's test
Full Information
NCT ID
NCT04080232
First Posted
July 4, 2019
Last Updated
April 27, 2023
Sponsor
University Hospital, Bordeaux
Collaborators
SFGM-TC
1. Study Identification
Unique Protocol Identification Number
NCT04080232
Brief Title
Study of Pulmonary MRI for the Diagnosis of Bronchiolitis Obliterans Syndrome After Allogeneic Stem Cell Transplantation
Acronym
IRM-A
Official Title
Study of Pulmonary MRI for the Diagnosis of Bronchiolitis Obliterans Syndrome After Allogeneic Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2020 (Actual)
Primary Completion Date
September 24, 2023 (Anticipated)
Study Completion Date
September 24, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
SFGM-TC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Bronchiolitis Obliterans Syndrome (BOS) is a major complication of Hematopoietic Stem cell Transplantation (HSCT) occurring in the context of chronic GVHD and associated with a poor prognosis. The diagnosis of BOS is based on functional (Pulmonary Functional Tests) and morphological criteria (chest CT-scan). Early diagnosis of BOS represents an unmet need and would facilitate early therapeutic interventions. Lung MRI has been recently developed with new sequences facilitating morphological and functional lung analysis in various inflammatory contexts. The goal of this study is to compare the morphological performances of chest CT-scan and MRI
Detailed Description
Patients undergoing allogeneic stem cell transplantation may develop non-infectious respiratory complication related to chronic graft versus host disease and called bronchiolitis obliterans syndrome (BOS). The occurrence of BOS is associated with a decreased survival reaching 13% at 5 years (Dudek et al, BBMT 2003). Thus, screening and diagnosis of BOS appear as a priority of post-transplant patients monitoring, in order to begin early therapy if needed. To this end, patients undergo systematic and regular screening using pulmonary function tests (PFTs). In case of abnormal PFTs, tests are completed the screening of respiratory infections and chest computed tomographic scan (CT-scan) is performed. A report from the National Institute of Health described the following criteria required for the diagnosis of BOS : FEV1/vital capacity < 0.7, FEV1 < 75% or a decline >/= 10% from baseline, residual volume > 120%, absence of documented infection, and the presence of CT-scan signs suggestive of BOS : air trapping by expiratory CT or small airway thickening or bronchiectasis.
BOS severity depends on the development of fibrotic and fixed damages, poorly responding to therapies. New tools are needed in order to favor early BOS diagnosis.
A recent study from our center showed that repeated CT-scans in stem cell transplant patients is associated with increased risk of neoplasia. In addition, recent studies from our center evaluated the use of pulmonary MRI providing good performance without X-ray exposure (Dournes G et al, Radiology 2015 et Dournes G et al, Eur Radiol 2015).
More recently, Renne et al (Radiology 2015) studied the performance of pulmonary MRI coupled with oxygen transfer analysis for the diagnosis of chronic lung allograft dysfunction. This study showed altered imaging parameters in patients developing BOS, including patients with early BOS stage (0p stage).
As pathogenic mechanisms seem to be shared between post-stem cell transplant and post-lung transplant BOS, we hypothesize that pulmonary MRI with oxygen transfer analysis and ultra short echo time may represent a non-invasive, non-irradiating and sensitive research tool for the detection and quantification of pulmonary lesions in patients screened for post-stem cell transplant BOS.
Thus, 20 patients who underwent allogeneic stem cell transplantation and show abnormal respiratory function over a 2 year period study are expected. They will be included according to the following criteria : age > 18 yo, > 3 months post-transplant, absence of documented pulmonary infection, or with a minimum of 6 weeks after a documented pulmonary infection, and the following BOS criteria : abnormal PFTs (FEV1/VC < 0.7, FEV1 < 0.75, residual volume < 120% of expected value) and/or chest CT-scan showing air trapping or small airway thickening. Similarly to lung transplant criteria, stage 0p BOS defined according to FEF25-75 values (Estenne et al, JHLT 2002), for which pulmonary MRI with oxygen transfer may guide to early BOS diagnosis, will be added.
Patients who give their consent will perform a pulmonary MRI, in the absence of contraindication, using different sequences to evaluate morphologic and functional performances of pulmonary MRI. We will compare CT-scan and MRI performances using blinded analysis from two radiologists.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiolitis Obliterans
Keywords
lung MRI performance, UTE, quantification, oxygen transfer, Bronchiolitis Obliterans syndrome, allogeneic stem cell transplantation
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lung MRI
Arm Type
Experimental
Arm Description
lung MRI concordance as compared to chest CT-scan for the description of morphological abnormalities necessary for the diagnosis of BOS after HSCT. It will be evaluated using lung MRI performed after inclusion (D0) using a standardized procedure
Intervention Type
Device
Intervention Name(s)
lung MRI
Intervention Description
lung MRI (1.5T Siemens Aera) using the following sequences: 3D Fast gradient-echo pulse sequences with ultra-short echo time (UTE), acquisitions at end-inspiration breath hold, end-expiration breath hold, and free-breathing using an echonavigator positioned on the diaphragm, acquisitions using routine pulse sequences (SSFP, T2FSE) and the administration of oxygen during the MRI: O2 will be administered at 15L/min during 6 minutes.
Primary Outcome Measure Information:
Title
lung MRI concordance as compared to chest CT-scan
Description
lung MRI concordance as compared to chest CT-scan for the description of morphological abnormalities necessary for the diagnosis of BOS after HSCT. It will be evaluated using lung MRI performed after inclusion (Baseline) using a standardized procedure. The agreement between MRI and chest CT-scan for the presence or absence of the following features, will be measured at the segmental level: airway thickening, bronchiectasis, air trapping.
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Bhalla Score precision in morphological MRI
Description
Measure of Bhalla Score precision in morphological MRI for the diagnosis of post-transplant BOS
Time Frame
Baseline
Title
Bhalla Score in CT scan
Description
Bhalla Score in CT scan
Time Frame
Baseline
Title
oxygen transfer capacity
Description
Measure of oxygen transfer capacity (percentage of intra-pulmonary signal variation before and after inhalation of oxygen);
Time Frame
Baseline
Title
Force Expiratory Volume
Description
Force Expiratory Volume (FEV, l)
Time Frame
Baseline
Title
FEV1/VC
Description
FEV1/VC (Tiffeneau),
Time Frame
Baseline
Title
Residual volume
Description
Residual volume (l)
Time Frame
Baseline
Title
total lung capacity
Description
Total lung capacity (l)
Time Frame
Baseline
Title
BOS stages
Description
BOS stages (0 : FEV1 > 90%, and FEF25-75 > 75% from baseline; 0p : 10-19% decrease in FEV1, and/or by a >/= 25% decrease in FEF 25-75 from baseline; 1: FEV1 60-79% ; 2: FEV1 40-59% ; 3: FEV1</= 39)
Time Frame
Baseline
Title
intra-observer repeatability of the Bhalla score in CT scan
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
Title
intra-observer repeatability of the Bhalla score in MRI
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
Title
intra-observer repeatability of the measure of oxygen transfer capacity
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
Title
inter-observer reproducibility of the Bhalla score in CT scan
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
Title
inter-observer reproducibility of the Bhalla score in MRI
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
Title
inter-observer reproducibility of the measure of oxygen transfer capacity
Description
Intraclass coefficient and Bland-Altman's test
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient ≥ 18 yo ;
Patient who underwent an allogeneic stem cell transplantation (SCT)
> 3 months post-SCT
With evidence of
respiratory symptoms, and/or
Pathological PFTs defined by : obstructive syndrome (FEV1 :vital capacity/CVF < 0.7), FEV1 < 0.75 of pre-SCT values, residual volume > 120%, and/or ;
Altered PFTs consistent with 0p stage described in lung transplantation BOS: FEV1 decline ≥ 10 % and/or FEF25-75 decline ≥ 25% compared to pre-SCT PFTs, and/or ;
Abnormal chest CT-scan with findings consistent with BOS: evidence of air trapping on expiratory CT-scan, bronchiectasis, and/or airway thickening.
Exclusion Criteria:
Contraindication for MRI ;
Contraindication of oxygen administration ;
Decompensation of altered respiratory function ;
Acute respiratory infection (bacterial, fungal or viral) documented in the last 6 weeks ;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Edouard Forcade, MD
Phone
335 57 65 65 11
Email
edouard.forcade@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Elodie Blanchard, MD
Email
elodie.blanchard@chu-bordeaux.fr
Facility Information:
Facility Name
CHU Bordeaux
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edouard Forcade, MD
Email
edouard.forcade@chu-bordeaux.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Pulmonary MRI for the Diagnosis of Bronchiolitis Obliterans Syndrome After Allogeneic Stem Cell Transplantation
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