Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI

NCT01832363 | Completed Phase 2 DMC

• 2 other identifiers: MagniXene-112397R44HL112397
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Asthma

Keywords

Severe asthma; Bronchial thermoplasty; MagniXene; Hyperpolarized Xenon; HXe; HyXe

Outcome Measures

Primary Outcomes (1)

• Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline

  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).

  2.5 years

Secondary Outcomes (1)

• Assessment of HXe MRI as an imaging biomarker for asthma disease severity

  2.5 years

Study Arms (2)

HXe MRI guided treatment sequence for BT

EXPERIMENTAL

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

Standard treatment sequence for BT (control)

ACTIVE COMPARATOR

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)

Interventions

HXe MRI guided treatment sequence for BT DRUG

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).

Also known as: MagniXene, Hyperpolarized Xenon, HXe

HXe MRI guided treatment sequence for BT

Standard treatment sequence for BT (control) OTHER

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.

Also known as: MagniXene, Hyperpolarized Xenon, HXe

Standard treatment sequence for BT (control)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Xemed LLC: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Washington University School of Medicine: collaborator
• University of Virginia: collaborator

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Iulian C Ruset, PhD

  Xemed LLC

  PRINCIPAL INVESTIGATOR

• James Quirk, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Nicholas Tustison, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 16, 2013
• Study Start: March 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: May 1, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-01

Locations

US (1)