Clinical trial NCT02075151: Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype
Official title: Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Asthma
Keywords: Bronchial Thermoplasty
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2014-03-03
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: According to World Health Organization (WHO) estimates, more than 200 million people suffer from asthma worldwide and in 2009, the disease had claimed 250,000 lives globally. Autopsy reports suggest 2 phenotypes of severe asthma: one that is characterized by intense airway inflammation with mucus plugging, and the other by severe bronchoconstriction causing respiratory failure in the absence of significant airway inflammation. However, it is not easy to stratify patients according to phenotypes without bronchoscopy. Although severe asthma comprises only 10% of affected individuals, it accounts for more than half of the total healthcare spending on asthma. Inhaled corticosteroids are effective by suppressing production of multiple pro-inflammatory mediators, unfortunately efficacy plateaus. Addition of long acting beta agonist and anti-cholinergic agent to inhaled corticosteroids offers some measure of relief but effective treatment of severe asthma remains an unmet goal, resulting in intensive utilization of healthcare resources. In 2010, the United States Food and Drug Administration (FDA) approved bronchial thermoplasty (BT) as an adjunctive therapy for severe asthma. BT is radiofrequency ablation of airway smooth muscle via bronchoscopy with each patient undergoing three procedures which targets different lobes of the lung 3 weeks apart. Studies have demonstrated improved symptom control allowing discontinuation of oral steroids in some patients as well as reductions in exacerbations, hospitalizations and use of rescue medications. No development of airway strictures or bronchiectasis, and regeneration of normal epithelium after BT has been observed. At present, it remains unclear if BT benefits all asthma phenotypes or if BT has any effect on airway inflammation and remodeling.

The hypothesis of this study is that bronchial thermoplasty is likely to benefit all severe asthma phenotypes, and achieves this by exerting an effect on airway inflammation and remodelling.

The specific aims of the study are: 1) to better define the asthma phenotype who will benefit from BT by microarray and gene expression profiling; 2) to study effects of BT on airway inflammation; 3) to define its role in the overall asthma management algorithm


Eligibility criteria: Inclusion Criteria:

* Males and females between 21-65 years of age
* Poorly controlled severe persistent asthma (ACT score \< 20) despite high-dose inhaled steroids (\>500 mcg fluticasone/day or \>800 mcg budesonide/day) in combination with inhaled long-acting Beta-2 agonist and/or anticholinergic agent. Other drugs include leukotriene modifiers, omalizumab (if used for at least 1 year prior), and oral corticosteroids 10mg/day or less
* Stopped smoking for \> 1 year and \<10 pack-years
* Stable maintenance asthma medications for 4 weeks
* Pre-bronchodilator FEV1 \>60% predicted

Exclusion Criteria:

* Males and females \<21 and \>65 years of age
* Presence of pacemaker, internal defibrillator, or other implantable electronic devices
* Known sensitivity to medications required to perform bronchoscopy, including lignocaine and benzodiazepines
* Patients previously treated with Bronchial Thermoplasty (BT)
* Use of immunosuppressant (excluding oral steroids)
* Increased risk of adverse events associated with bronchoscopy or anesthesia (including pregnancy, uncontrolled coronary artery disease, acute or chronic renal failure, and uncontrolled hypertension)
* Inability to cease antiplatelet or anticoagulant therapy prior to procedure

Primary outcomes:
measure: Asthma Control Test (ACT) score
timeFrame: Up to 2 years
Secondary outcomes:
measure: Percentage of symptom-free days
timeFrame: Up to 2 years
measure: Number of adverse events
timeFrame: Up to 2 years
measure: Peak Expiratory Flow (PEF)
timeFrame: Up to 2 years
measure: Exhaled nitric oxide (NO)
timeFrame: Up to 2 years
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Up to 2 years
measure: Non-contrast Computed Tomography (CT) scan of the thorax
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Kay Leong Khoo, MD
role: PRINCIPAL_INVESTIGATOR
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