Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype

Asthma Clinical Trial

Official title:

Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02075151
• Other study ID #: DSRB/2013/00144
• Status: Not yet recruiting
• Phase: N/A
• First received: February 13, 2014
• Last updated: February 26, 2014
• Start date: February 2014
• Est. completion date: May 2018

Study information

• Verified date: February 2014
• Source: National University Hospital, Singapore
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Domain Specific Review Boards
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 64 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Procedure:
• Bronchial Thermoplasty
Bronchial thermoplasty

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (18)

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Asthma Control Test (ACT) score		Up to 2 years	No
Secondary	Percentage of symptom-free days		Up to 2 years	No
Secondary	Number of adverse events		Up to 2 years	Yes
Secondary	Peak Expiratory Flow (PEF)		Up to 2 years	No
Secondary	Exhaled nitric oxide (NO)		Up to 2 years	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)		Up to 2 years	No
Secondary	Non-contrast Computed Tomography (CT) scan of the thorax		Up to 2 years	No