AsthmaPhase 2/3HXe-BTNCT01832363
Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
A Phase 2/3 study testing HXe MRI guided treatment sequence for BT in people with Asthma, run by Xemed LLC at 1 site in United States.
Trial summary
The purpose of this study is to determine if the bronchial thermoplasty treatment can be guided through hyperpolarized xenon lung MRI. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- HXe MRI guided treatment sequence for BT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to May 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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
- Obesity exceeding the scanner capability
- Metal implants or non-removable metal piercings
- Inability to tolerate MRI scanning due to claustrophobia
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University in St. Louis
St Louis, Missouri, 63110
About this study
Official title: Single-Session Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
The purpose of this study is to determine if the bronchial thermoplasty treatment can be guided through hyperpolarized xenon lung MRI.
Read the 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.
- Conditions
- Asthma
- Being tested
- HXe MRI guided treatment sequence for BT, Standard treatment sequence for BT (control)
- Keywords
- Severe asthma, Bronchial thermoplasty, MagniXene, Hyperpolarized Xenon, HXe, HyXe
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HXe MRI guided treatment sequence for BTDrug
Also called MagniXene, Hyperpolarized Xenon, HXe
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).
Standard treatment sequence for BT (control)Other
Also called MagniXene, Hyperpolarized Xenon, HXe
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Standard treatment sequence for BT (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2.5 years
Secondary outcomes (1)
Assessment of HXe MRI as an imaging biomarker for asthma disease severity
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.
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionDec 2018
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xemed LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Washington University School of Medicine, University of Virginia
- Responsible party
- Sponsor
- Investigators
- Iulian C Ruset, PhD, Principal investigator, Xemed LLCJames Quirk, PhD, Principal investigator, Washington University School of MedicineNicholas Tustison, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01832363
- Sponsor's protocol ID
- MagniXene-112397
- Other IDs
- R44HL112397
- Acronym
- HXe-BT
- Status last verified
- Jan 2019
- First submitted
- 28 Mar 2013
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Session Bronchial Thermoplasty for Severe Asthmatics Guided by HXe MRI
- ClinicalTrials.gov ID
- NCT01832363
- Acronym / sponsor ID
- HXe-BT / MagniXene-112397
- Conditions
- Asthma
- Keywords
- Severe asthma, Bronchial thermoplasty, MagniXene, Hyperpolarized Xenon, HXe, HyXe
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Xemed LLCIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Washington University School of Medicine, University of Virginia
- Study start
- Mar 2013 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 16 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HXe MRI guided treatment sequence for BT | Experimental | Drug: HXe MRI guided treatment sequence for BTPatients 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) | Active comparator | Other: 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (23 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HXe MRI guided treatment sequence for BTAlso: MagniXene, Hyperpolarized Xenon, HXeHXe 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). | Drug | HXe MRI guided treatment sequence for BT |
| Standard treatment sequence for BT (control)Also: MagniXene, Hyperpolarized Xenon, HXePatients 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 | Standard treatment sequence for BT (control) |
Primary outcome
Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline
Time frame: 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).
1 secondary outcome
Assessment of HXe MRI as an imaging biomarker for asthma disease severity
Time frame: 2.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iulian C Ruset, PhD principal investigator
Xemed LLC
James Quirk, PhD principal investigator
Washington University School of Medicine
Nicholas Tustison, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing HXe MRI guided treatment sequence for BT in people with Asthma, run by Xemed LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Asthma Quality of Life Questionnaire (AQLQ) from baseline (time frame: 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.