Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): HXe MRI guided treatment sequence for BT; Standard treatment sequence for BT (control)
Intervention type(s): Drug; Other
Intervention description(s): 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).; 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.
Other intervention name(s): MagniXene; Hyperpolarized Xenon; HXe; MagniXene; Hyperpolarized Xenon; HXe
Intervention MeSH terms: Xenon
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Severe asthma; Bronchial thermoplasty; MagniXene; Hyperpolarized Xenon; HXe; HyXe