Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI

Phase 2

Completed

• Conditions: Asthma
• Interventions: Drug: HXe MRI guided treatment sequence for BT; Other: Standard treatment sequence for BT (control)

• Registration Number: NCT01832363
• Lead Sponsor: Xemed LLC

Brief Summary

The purpose of this study is to determine if the bronchial thermoplasty treatment can be guided through hyperpolarized xenon lung MRI.

Detailed Description

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 whether the standard full BT treatment is superior to a single session guided treatment. The statistical metric will be the incremental change in the AQLQ score.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-28
• Study First Submitted QC: 2013-04-15
• Study First Posted: 2013-04-16
• Primary Completion: 2018-12
• Status Verified: 2019-01
• Study Completion: 2019-05
• Last Update Submitted: 2019-08-23
• Last Update Posted: 2019-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HXe MRI guided treatment sequence for BT	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.
Standard treatment sequence for BT (control)	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.

Primary Outcome Measures

Name	Time	Method
Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline	2.5 years	Asthma Quality of Life Questionnaire (AQLQ) is the primary outcome of this study. We will test whether the standard (unguided) three session BT treatment is superior to the a HXe MRI guided, single session BT treatment. 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).

Secondary Outcome Measures

Name	Time	Method
Assessment of HXe MRI as an imaging biomarker for asthma disease severity	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.

Trial Locations

Locations (1)

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States