Clinical trial NCT01832363: Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
Official title: Single-Session Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Asthma
Keywords: Severe asthma
Bronchial thermoplasty
MagniXene
Hyperpolarized Xenon
HXe
HyXe
Lead sponsor: Xemed LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Washington University School of Medicine
name: University of Virginia
First posted: 2013-04-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria (bronchial thermoplasty):

* Males or females age 18 or greater and less than 65.
* 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.
* Asthma exacerbation requiring hospitalization during the prior six weeks.
* 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, untreated 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
* Hemoglobin level below 10 g/dl as determined in a recent (within 12 months) measurement

Primary outcomes:
measure: Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline
timeFrame: 2.5 years
Secondary outcomes:
measure: Assessment of HXe MRI as an imaging biomarker for asthma disease severity
timeFrame: 2.5 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Xemed LLC
name: Iulian C Ruset, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: James Quirk, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Nicholas Tustison, PhD
role: PRINCIPAL_INVESTIGATOR
References: