Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI (HXe-BT)

This study is currently recruiting participants.
Verified April 2013 by Xemed LLC
Sponsor:
Collaborators:
Washington University School of Medicine
University of Virginia
Information provided by (Responsible Party):
Xemed LLC
ClinicalTrials.gov Identifier:
NCT01832363
First received: March 28, 2013
Last updated: April 15, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Asthma
Drug: HXe MRI guided treatment sequence for BT
Other: Standard treatment sequence for BT (control)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Single-Session Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI

Resource links provided by NLM:


Further study details as provided by Xemed LLC:

Primary Outcome Measures:
  • Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Assessment of HXe MRI as an imaging biomarker for asthma disease severity [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 30
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Other Names:
  • MagniXene
  • Hyperpolarized Xenon
  • HXe
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.
Other Names:
  • MagniXene
  • Hyperpolarized Xenon
  • HXe

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (bronchial thermoplasty):

  • Subject has asthma and is taking regular maintenance medication for past 12 months that includes:

    • Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting ß2-agonist (LABA) at a dosage of ≥100μg per day Salmeterol or equivalent.
    • Other asthma medications such as leukotriene modifiers, or anti-immunoglobulin E (IgE), are acceptable (Subjects on Xolair® must have been on Xolair for greater than 1 year).
  • Asthma confirmed by: (a) b-agonist reversibility of FEV1 ≥ 12 % following 360mcg albuterol OR (b) 20% fall in forced expiratory volume in 1 second (PC20-FEV1) after a challenge with methacholine ≤ 8 mg/ml if not receiving an inhaled corticosteroid (ICS) or ≤ 16 mg/ml if receiving an ICS.
  • FEV1 ≥ 50% predicted pre-bronchodilator.
  • Asthma symptoms on at least two days or one night per week over the last 2 weeks.
  • Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack-years total smoking history).
  • Patient has a clinical indication for bronchial thermoplasty as decided by their treating physician.
  • Ability to undergo bronchoscopy in the opinion of the investigator.

Exclusion Criteria (bronchial thermoplasty):

  • Asthma exacerbation (ED visit, hospitalization, course of increased systemic steroids, or urgent health care visit for asthma) during the prior four weeks.
  • Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year or 1 or more ICU admission for asthma in the previous year.
  • Chronic oral steroid therapy greater than 30 mg per day.
  • Respiratory tract infection within past 4 weeks
  • Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
  • Subject is undergoing immunosuppressant therapy (e.g., methotrexate).
  • Subject is on anticoagulant medication.
  • Subject has bleeding diathesis, platelet dysfunction, and thrombocytopenia with platelet count less than 125,000/mm2 or known coagulopathy (INR > 1.5).
  • Subject has other respiratory diseases including interstitial lung disease, emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, obstructive sleep apnea, Churg-Strauss syndrome, cardiac dysfunction, and allergic bronchopulmonary aspergillosis (total IgE of >1000 Units/mL with positive specific IgE to aspergillus and evidence of central bronchiectasis).
  • Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray.
  • Subject has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysrhythmia, conduction defect, cardiomyopathy, aortic aneurysm, or stroke.
  • Subject has uncontrolled hypertension (>200mm Hg systolic or >100mm Hg diastolic pressure).
  • Subject uses an internal or external pacemaker or cardiac defibrillator.
  • Chronic diseases (other than asthma) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, or nervous system, or immunodeficiency
  • History of cigarette smoking with > 10 pack years total
  • Use of investigative drugs or intervention trials in the 30 days prior to enrollment or during the duration of the study
  • Any condition or compliance issue which in the opinion of the investigator might interfere with participation in the study

Exclusion Criteria (Magnetic Resonance Imaging):

  • Obesity exceeding the scanner capability
  • Metal implants or non-removable metal piercings
  • Inability to tolerate MRI scanning due to claustrophobia

Exclusion Criteria (HXe inhalation):

  • Pregnancy or intention to become pregnant
  • Neurological or cardiac comorbidities
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01832363

Contacts
Contact: Iulian C Ruset, PhD 603-868-1888 ext 113 icruset@xemed.com
Contact: F. W Hersman, PhD 603-868-1888 hersman@xemed.com

Locations
United States, Missouri
Washington University in St. Louis Recruiting
St. Louis, Missouri, United States, 63110
Contact: James Quirk, PhD    314-362-3875    quirkj@mir.wustl.edu   
Contact: Lora Gallagher, B.S.    314-747-4065    gallagherl@wustl.edu   
Sub-Investigator: Mario Castro, MD, M.P.H.         
Principal Investigator: James Quirk, PhD         
Sub-Investigator: Jason C Woods, PhD         
Sponsors and Collaborators
Xemed LLC
Washington University School of Medicine
University of Virginia
Investigators
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
  More Information

No publications provided

Responsible Party: Xemed LLC
ClinicalTrials.gov Identifier: NCT01832363     History of Changes
Other Study ID Numbers: MagniXene-112397, R44HL112397
Study First Received: March 28, 2013
Last Updated: April 15, 2013
Health Authority: United States: Food and Drug Administration
United States: National Institutes of Health
United States: NHLBI

Keywords provided by Xemed LLC:
Severe asthma
Bronchial thermoplasty
MagniXene
Hyperpolarized Xenon
HXe
HyXe

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Xenon
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014