Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype

February 26, 2014 updated by: National University Hospital, Singapore

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore
        • National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 64 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Bronchial Thermoplasty
Bronchial thermoplasty
Procedure: Bronchial Thermoplasty
Bronchial thermoplasty

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Asthma Control Test (ACT) score
Time Frame: Up to 2 years
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of adverse events
Time Frame: Up to 2 years
Up to 2 years
Percentage of symptom-free days
Time Frame: Up to 2 years
Up to 2 years
Peak Expiratory Flow (PEF)
Time Frame: Up to 2 years
Up to 2 years
Exhaled nitric oxide (NO)
Time Frame: Up to 2 years
Up to 2 years
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Up to 2 years
Up to 2 years
Non-contrast Computed Tomography (CT) scan of the thorax
Time Frame: Up to 2 years
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Kay Leong Khoo, MD, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (ANTICIPATED)

May 1, 2018

Study Completion (ANTICIPATED)

May 1, 2018

Study Registration Dates

First Submitted

February 13, 2014

First Submitted That Met QC Criteria

February 26, 2014

First Posted (ESTIMATE)

March 3, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

March 3, 2014

Last Update Submitted That Met QC Criteria

February 26, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DSRB/2013/00144

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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