Clinical trial NCT02618551: Bronchial Thermoplasty for Severe Asthma With Dynamic Hyperinflation
Official title: Evaluation of the Efficiency of Bronchial Thermoplasty on Dynamic Hyperinflation in Uncontrolled Severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Hyperinflation
Keywords: Thermoplasty
Severe asthma
Dynamic hyperinflation
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-12-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Bronchial thermoplasty is a treatment for severe asthma that consist in decreasing the thickness of bronchial muscle by heat using a catheter inserted into the bronchi under direct vision with the help of an endoscope This treatment has shown efficacy on symptoms, quality of life and the number of exacerbations related to severe asthma.

This clinical study evaluates the efficiency of this treatment on the dynamic hyperinflation phenomenon (worsening of bronchial obstruction during exercise in patients with asthma contributing to worsening shortness of breath).

Detailed description: Bronchial thermoplasty is a recently validated bronchoscopic technique for the management of severe asthma that treats smooth muscle by radiofrequency to reduce its thickness. This procedure leads to improved asthma control and quality of life, but also to decreased exacerbations frequency and number of emergencies hospitalizations. This treatment requires 3 procedures every 3 to 4 weeks.

The pathophysiological mechanisms underlying its effectiveness need to be better understood for an improved selection of best candidates. In particular, there is a discrepancy between the improvement observed in symptoms (ACQ), quality of life (AQLQ) and the lack of improvement in forced expiratory volume in 1 second (FEV1). Investigator assume that this paradox is due to an efficiency appearing at effort, targeting dynamic hyperinflation phenomenon.

The objective of this study is to evaluate the influence of bronchial thermoplasty on dynamic hyperinflation in severe asthma. The secondary objectives are to assess the effectiveness of bronchial thermoplasty (ACQ, AQLQ) in a selected population of patients with dynamic hyperinflation and to describe bronchial wall structural changes by probe-based confocal LASER endomicroscopy (pCLE).

Eligibility criteria: Inclusion Criteria:

* Severe asthma, uncontrolled despite optimal treatment according to GINA (global initiative for asthma) recommendations
* At least 2 exacerbations treated by systemic steroids in the last year
* FEV1 between 40 and 80% of predicted values and dynamic hyperinflation (defined as a decrease in inspiratory capacity by more than 500 ml during exercise)

Exclusion Criteria:

* Current asthma exacerbation or respiratory infection
* History of exacerbation after bronchoscopy
* FEV1 \< 40% of predicted values
* Oxygen saturation \< 90%
* Contra-indications to ALAIR catheter system : pacemaker or other electronic implanted device
* Allergy to Remifentanyl or Propofol
* pregnancy; breastfeeding

Primary outcomes:
measure: Evolution of dynamic hyperinflation
timeFrame: 3 months
Secondary outcomes:
measure: Structural modification of the bronchial wall
timeFrame: 3 months
measure: Efficiency of bronchial thermoplasty on asthma
timeFrame: 3 months
measure: Assess side effects
timeFrame: 3 months
Other outcomes:
Locations:
city: Toulouse
country: France
facility: DIDIER Alain
state: Midi Pyrenees
Study officials:
affiliation: Toulouse Rangueil Larrey University Hospital
name: Alain DIDIER, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, Calhoun WJ, Castro M, Chung KF, Clark MP, Dweik RA, Fitzpatrick AM, Gaston B, Hew M, Hussain I, Jarjour NN, Israel E, Levy BD, Murphy JR, Peters SP, Teague WG, Meyers DA, Busse WW, Wenzel SE; National Heart, Lung, Blood Institute's Severe Asthma Research Program. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007 Feb;119(2):405-13. doi: 10.1016/j.jaci.2006.11.639.
citation: Brown RH, Wizeman W, Danek C, Mitzner W. Effect of bronchial thermoplasty on airway distensibility. Eur Respir J. 2005 Aug;26(2):277-82. doi: 10.1183/09031936.05.00006605.
citation: Cox G, Thomson NC, Rubin AS, Niven RM, Corris PA, Siersted HC, Olivenstein R, Pavord ID, McCormack D, Chaudhuri R, Miller JD, Laviolette M; AIR Trial Study Group. Asthma control during the year after bronchial thermoplasty. N Engl J Med. 2007 Mar 29;356(13):1327-37. doi: 10.1056/NEJMoa064707.
citation: Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M; RISA Trial Study Group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91. doi: 10.1164/rccm.200704-571OC. Epub 2007 Sep 27.
citation: Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Duhamel DR, McEvoy C, Barbers R, Ten Hacken NH, Wechsler ME, Holmes M, Phillips MJ, Erzurum S, Lunn W, Israel E, Jarjour N, Kraft M, Shargill NS, Quiring J, Berry SM, Cox G; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010 Jan 15;181(2):116-24. doi: 10.1164/rccm.200903-0354OC. Epub 2009 Oct 8.
citation: Wechsler ME, Laviolette M, Rubin AS, Fiterman J, Lapa e Silva JR, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Hales JB, McEvoy C, Slebos DJ, Holmes M, Phillips MJ, Erzurum SC, Hanania NA, Sumino K, Kraft M, Cox G, Sterman DH, Hogarth K, Kline JN, Mansur AH, Louie BE, Leeds WM, Barbers RG, Austin JH, Shargill NS, Quiring J, Armstrong B, Castro M; Asthma Intervention Research 2 Trial Study Group. Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013 Dec;132(6):1295-302. doi: 10.1016/j.jaci.2013.08.009. Epub 2013 Aug 30.
citation: Guibert N, Guilleminault L, Lepage B, Heluain V, Fumat R, Dupuis M, Faviez G, Plat G, Hermant C, Didier A. Bronchial thermoplasty in patients with dynamic hyperinflation: results from the proof-of-concept HEAT trial. Eur Respir J. 2021 Jan 28;57(1):2001616. doi: 10.1183/13993003.01616-2020. Print 2021 Jan. No abstract available.