Bronchial Thermoplasty: Effect on Neuronal and Chemosensitive Component of the Bronchial Mucosa (BT-ASMN)

• ClinicalTrials.gov Identifier: NCT01839591
• Recruitment Status: Unknown
• First Posted: April 25, 2013
• Last Update Posted: April 1, 2014
• Sponsor: Arcispedale Santa Maria Nuova-IRCCS
• Information provided by (Responsible Party): Nicola Facciolongo, Arcispedale Santa Maria Nuova-IRCCS

Study Description

Brief Summary:

In severe bronchial asthma the mechanism of inflammation and bronchospasm is complex and still not clarified. The smooth muscle cells play an important role from the mechanical point of view, as a culmination of neurogenic stimuli and inflammatory cytokines that determine as final effect the bronchospasm and over time a hypertrophy of the muscular coat. There are some other hypothesis that the smooth muscle cells may play a role as central regulator of chemical mediators that cause bronchospasm and inflammation, although there are currently no firm conclusions 2 According to other studies3,the nerve receptors TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 have a great importance in the complex mechanism of airway inflammation too. (There are at least 4)

These receptors would intervene according to the following mechanism:

1. Irritants on the bronchial mucosa stimulate the TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 present on afferent endings of sensory fibers, unmyelinated C (chemiosensitive neurons)
2. On the same afferent axon acting factors with the activation effect (lowering the activation threshold, increase the expression, promote the translocation of TRPV1 receptor on the membrane). Among these factors the neurotrophins of which the most important NERVE GROWTH FACTOR (NGF)

3. The activation of TRPV1 (through release of Ca2 + +) determines two efferent responses:

   1. CENTRALLY-MEDIATED
   2. LOCAL AXON Reflex

Investigators hypothesized that BT may have a strong influence on the destruction of nerve receptors TRPV1 and unmyelinated nerve fibers located in the mucosa going to stop reflections both central and local authorities responsible for the activation of bronchospasm. In support of this hypothesis, there are some anatomical studies4, which show that these receptors are more numerous at the level of main bronchi which are the main target of BT. Please note in this context that it is already known that in thermoablations commonly used in cardiology it is used a radio frequency with development of heat controlled to 65 °, as in the BT, able to interrupt the circuit nervous responsible for the activation of the circuit causing the abnormal 'arrhythmia.

Condition or disease	Intervention/treatment	Phase
Severe Persistent Asthma	Device: catheter ALAIR	Not Applicable

Detailed Description:

The mechanism of action the bronchial thermoplasty exerts the positive action demonstrated by the studies through is not yet well understood yet. The only action on the denaturation and destruction of the smooth muscle layer of the bronchi at intermediate and high caliber perhaps not fully explain its action, taking into account that most of the smooth muscle loading of the small airways is minimally altered by the procedure. From the premises outlined in the section on the mechanism of inflammation we hypothesized that BT may have a strong influence on the destruction of nerve receptors TRPV1 and unmyelinated nerve fibers located in the mucosa going to stop reflections both central and local authorities responsible for the activation of bronchospasm. In support of this hypothesis, there are some anatomical studies4, which show that these receptors are more numerous at the level of main bronchi which are the main target of BT. Please note in this context that it is already known that in thermoablations commonly used in cardiology it is used a radio frequency with development of heat controlled to 65 °, as in the BT, able to interrupt the circuit nervous responsible for the activation of the circuit causing the abnormal 'arrhythmia.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Treatment of Bronchial Severe Asthma With Bronchial Thermoplasty. Assessment of Efficacy and Safety of Treatment, Study of Effects on Neuronal and Chemosensitive Component of the Bronchial Mucosa Pre and Post Treatment
• Study Start Date: March 2013
• Estimated Primary Completion Date: April 2015
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bronchial Thermoplasty; bronchoscopy bronchial thermoplasty catheter ALAIR Boston SCientific asthma	Device: catheter ALAIR; Catheter ALAIR Radiofrequency 65°; Other Names: Catheter ALAIR Boston Scientific; M005ATS25010 MOd ATS 2-5

Outcome Measures

Primary Outcome Measures :

1. analysis of the risk and benefit profile with questionnaire ACT and AQLQ [ Time Frame: Change from Baseline in ACT and AQLQ Questionaire one year after the end of the procedure ]

   Evaluation of symptom control through the questionnaire ACT (ASTHMA CONTROL TEST) and AQLQ (Asthma quality life Questionaire) according to GINA criteria.

   The questionnaires AQLQ and ACT will be collected 3 months before the TB, the day before the procedure, and 3, 6, 12 months after the end of the procedure.

Secondary Outcome Measures :

1. Analyze the changes in the state of innervation and nerve receptors before and after BT on histological samples of the bronchial mucosa [ Time Frame: biopsies every 4 weeks( during the treatment) ]
   first biopsies in left lower lobe non yet treated; second biopsies in right lower lobe already treated; third biopsies in upper lobe already treated;

Other Outcome Measures:

1. Evaluate the effect of BT on the run neurogenic inflammation by analysis of the chemical mediators of inflammation on histological samples of the bronchial mucosa. [ Time Frame: biopsies every 4 weeks (during the treatment) ]
   first biopsies in left lower lobe non yet treated; second biopsies in right lower lobe already treated; third biopsies in upper lobe already treated;

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient with severe persistent asthma uncontrolled found in stable for at least 3 weeks
2. Patient receiving regular treatment with inhaled corticosteroids (beclomethason> 1000 mcg or equivalent) and LABA (salmeterol> = 100 mcg or equivalent)
3. AQLQ score <6.25
4. FEV1> = 60% predicted
5. Patients not smoking for at least one year

Exclusion Criteria:

1. acute asthma with life threatening
2. concomitant respiratory diseases (eg, COPD or emphysema)
3. use of ß-blocker drugs
4. severe active infection in the last 2 weeks
5. Pacemaker, internal defibrillator or other implanted electronic device.
6. Known sensitivity to medications used to perform bronchoscopy, including lidocaine, atropine and benzodiazepines.
7. Currently known bleeding disorder is not well controlled.
8. Inability to stop prior to the procedure taking anticoagulants, antiplatelet agents, aspirin or non-steroidal anti-inflammatory drugs
9. 18 years
10. Pregnant women

Contacts and Locations

Contacts

Contact: Nicola Facciolongo NF Facciolongo, M D; 0522-295956 ext +39; nicola.facciolongo@asmn.re.it

Contact: Carla CG Galeone, phD; carla.galeone@asmn.re.it

Locations

Italy

REGGIO EMILIA IRCCS, Santa Maria Nuova Hospital; Recruiting

Reggio Emilia, Italy, 42024

Contact: Nicola NF Facciolongo, MD 0522-295956 ext +39 nicola.facciolongo@asmn.re.it

Principal Investigator: Nicola NF Facciolongo, MD

Sub-Investigator: Roberto RP Piro, MD

Sub-Investigator: Gianluigi GB Bajocchi, MD

Sub-Investigator: Francesco FM Menzella, MD

Sub-Investigator: Claudia CC Castagnetti, MD

Sub-Investigator: Alberto AC Cavazza, MD

Sub-Investigator: Vladimiro VP Pietrini, MD

Sub-Investigator: Luisa LS Savoldi, Statistics

Sub-Investigator: Carla CG Galeone, Biologist

Sponsors and Collaborators

Arcispedale Santa Maria Nuova-IRCCS

Investigators

• Principal Investigator: Nicola NF Facciolongo, M.D.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Facciolongo N, Di Stefano A, Pietrini V, Galeone C, Bellanova F, Menzella F, Scichilone N, Piro R, Bajocchi GL, Balbi B, Agostini L, Salsi PP, Formisano D, Lusuardi M. Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma. BMC Pulm Med. 2018 Feb 8;18(1):29. doi: 10.1186/s12890-017-0554-8.

• Responsible Party: Nicola Facciolongo, medical doctor, Arcispedale Santa Maria Nuova-IRCCS
• ClinicalTrials.gov Identifier: NCT01839591
• Other Study ID Numbers: BT-01-ASMN
• First Posted: April 25, 2013
• Last Update Posted: April 1, 2014
• Last Verified: March 2014

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases