Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI (HXe-BT)
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|ClinicalTrials.gov Identifier: NCT01832363|
Recruitment Status : Recruiting
First Posted : April 16, 2013
Last Update Posted : January 9, 2018
|Condition or disease||Intervention/treatment||Phase|
|Asthma||Drug: HXe MRI guided treatment sequence for BT Other: Standard treatment sequence for BT (control)||Phase 1 Phase 2|
This study explores the feasibility of using hyperpolarized xenon (HXe) Magnetic Resonance Imaging (MRI) as a diagnostic imaging agent to prioritize the order of airway treatment by bronchial thermoplasty, rather than the FDA approved pre-established treatment sequence that is performed today.
The Alair® Bronchial Thermoplasty System is an FDA approved device clinically proven to be effective in treating severe asthma patients who are not well controlled with inhaled corticosteroids and long acting beta agonists. Bronchial thermoplasty (BT) is a procedure that reduces excessive airway smooth muscle by radio wave ablation, thus decreasing the ability of the airways to constrict during an asthma attack. The BT procedure is performed in three separate outpatient treatment sessions, each treating pre-established regions of the lungs. The sessions are separated by at least three weeks healing time.
MagniXene® is pure xenon gas which is magnetically altered to become a contrast agent for magnetic resonance imaging of the lungs. The subject inhales the hyperpolarized xenon while inside the MRI scanner and a highly detailed ventilation map of the lung spaces is acquired during a short breath-hold. By detecting unventilated regions and airway reactivity using HXe images, a prioritized scheme for performing bronchial thermoplasty can be elaborated to treat the most problematic airways within the first BT session. In this study the rest of the airway will be treated in the following two sessions, such that all the airways are treated in the end as in the standard procedure.
This study will include approximately 30 patients clinically indicated to undergo bronchial thermoplasty. Half of the patients will be randomly assigned to receive HXe guided BT, while the other half will receive standard BT procedure. HXe images and clinical measures of asthma disease severity, such as Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), morning expiratory peak flow (AM-PEF), pulmonary function tests (PFT), will be acquired at three time points interleaved with the BT sessions: before BT, 12 weeks after first session of BT, and 12 weeks after the third session of BT (approximately 36 weeks from baseline). HXe MRI will be repeated within the same day after bronchodilator treatment of the patient to establish airways reactivity. Additionally, a three-week follow up for HXe MRI will allow us to study temporal variability of HXe metrics. A total of six HXe imaging sessions (distinctive days), each including at least four HXe images will be dedicated to each patient.
The primary outcome of this study will be to determine to what extent the guided treatment is not inferior in benefit to the standard full treatment course. The statistical metric will be the incremental change in the AQLQ score.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||Single-Session Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI|
|Study Start Date :||March 2013|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2018|
Experimental: HXe MRI guided treatment sequence for BT
Patients in this arm will undergo bronchial thermoplasty treatment where the first session of the procedure will target the six most problematic airways as determined with HXe imaging. Patients will have the remaining of the airways treated in the two subsequent sessions.
Drug: HXe MRI guided treatment sequence for BT
HXe MRI consists in imaging the inhaled xenon gas inside the human lungs during a short breath-hold. High resolution 3D maps of the HXe distribution inside the lungs provide information regarding ventilation of the lungs, as the signal is proportional to the local concentration of HXe. A high MRI signal translates in unobstructed ventilation, while ventilation defects appear as dark regions on the map. HXe MRI will be performed pre and post bronchodilator in order to determine the airways which potentially are the most responsive to BT treatment. All HXe MRI images will be repeated within the same day for consistency check and after three weeks to study temporal variability. The reactivity of the airways will establish the treatment order, with the most problematic airways to be treated in the first BT session (not to exceed six).
Active Comparator: Standard treatment sequence for BT (control)
Patients in this arm will undergo standard treatment sequence of bronchial thermoplasty. To preserve the blind of the procedure to the subjects, the same timeline and clinical measures will be followed as for HXe guided patients.
Other: Standard treatment sequence for BT (control)
Patients undergoing standard BT procedure will have HXe MRI performed at time intervals similar to HXe MRI guided BT patients. While HXe images will not be used for guiding the sequence for airways to receive the BT treatment, metrics extracted from HXe images will be compared with clinically accepted asthma severity metrics (spirometry and asthma questionnaires) to assess HXe MRI as a biomarker for asthma severity.
- Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline [ Time Frame: 2.5 years ]Asthma Quality of Life Questionnaire (AQLQ) is the primary outcome of this study in demonstrating that the HXe MRI guided treatment, which can be accomplished in a single session, is not inferior in benefit to the standard three session bronchial thermoplasty treatment course. There will be three time points of measure of the AQLQ score: before the BT session (baseline), 12 weeks after the first BT session, and 12 weeks after the third (last) BT session (approximately 36 weeks from baseline).
- Assessment of HXe MRI as an imaging biomarker for asthma disease severity [ Time Frame: 2.5 years ]HXe MRI data analysis can quantify measures of lung functionality such as fractional ventilation (V) and bronchodilator response (BD), as well as temporal variability of these metrics (dV and dBD). These measures will be compared against existing clinical parameters defining asthma disease severity, such as questionnaire scores: AQLQ and Asthma Control Test; as well as spirometry measures: Forced Expiratory Volume in one second (FEV1), and morning Peak Expiratory Flow (AM-PEF), in search for correlations and to demonstrate that HXe can be considered a clinical measure for asthma disease severity.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01832363
|Contact: Iulian C Ruset, PhD||603-868-1888 ext email@example.com|
|Contact: F. W Hersman, PhDfirstname.lastname@example.org|
|United States, Missouri|
|Washington University in St. Louis||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: James Quirk, PhD 314-362-3875 email@example.com|
|Contact: Lora Gallagher, B.S. 314-747-4065 firstname.lastname@example.org|
|Sub-Investigator: Mario Castro, MD, M.P.H.|
|Principal Investigator: James Quirk, PhD|
|Principal Investigator:||Iulian C Ruset, PhD||Xemed LLC|
|Principal Investigator:||James Quirk, PhD||Washington University School of Medicine|
|Principal Investigator:||Nicholas Tustison, PhD||University of Virginia|