Assessing the Expression and the Activity of Rac1 Protein in the Airway Smooth Muscle of Asthmatic Patient

NCT03325088 | Completed

• 1 other identifier: RC16_0469
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is a chronic inflammatory respiratory disease affecting 6 to 7% of the French adult population and responsible of 1000 deaths in France every year. Many anti-inflammatory treatments are available but few had been developed to target hyperresponsiveness.Investigators and searchers of the Institut du thorax have recently demonstrated the main involvement of Rac1 monomeric G protein in the contraction of airway smooth muscle cells. They show that Rac1 is expressed in the airway smooth muscle cells in mice and its activity is increased in the bronchi of asthma induced mice sensitized to House-Dust Mite. They further demonstrate that Rac1 inhibition in mice by nebulisation reduces airway hyperresponsiveness and pulmonary inflammation. Investigators and searchers of the Institut du thorax would like to seek whether targeting Rac1 would be interesting in asthmatic patients. Primary objective of this study is to determine if Rac1 expression and activity in airway smooth muscle cells are increased in asthmatic patients compare to controlled samples (deceased donor samples). Secondary objective is to determine whether there is a correlation between Rac1 activity and asthma severity. If Rac1 activity in airway smooth muscles is indeed increased in asthmatic patients depending on asthma severity, Rac1 could be a potential target to treat airway hyperresponsiveness.

Conditions

Asthma

Keywords

Severe Asthma; airway smooth muscle cells; Rac1 protein

Outcome Measures

Primary Outcomes (1)

• Activity level and expression of Rac1 protein in airway smooth muscle cells of asthmatics vs non asthmatics samples

  Mean of fluorescence intensity of Rac1-GTP and Rac1 in paraffinised biopsies of airway smooth muscle cells

  at day 15

Secondary Outcomes (2)

• Assessing any difference between activity level and expression of Rac1 in airway smooth muscle cells of severe versus non severe asthmatic patients.

  at day 15

• Assessing any correlation between Rac1-GTP/Rac1 ratio signal, pulmonary function tests and clinical data

  at day 15

Study Arms (3)

Severe Asthma

OTHER

patients affected with severe asthma s defined by ERS-ATS (European Respiratory Society - American Thoracic Society) without long term oral corticosteroids treatment

Procedure: Bronchial endoscopy; Procedure: Bronchial biopsies; Procedure: Bronchial alveolar enema

Mild to moderate Asthma

OTHER

patients affected with untreated mild to moderate asthma

Procedure: Bronchial biopsies; Procedure: Bronchial alveolar enema

Controlled Sample

OTHER

smooth muscle cells from Tracheobronchial rings of non-asthmatic cadaveric donor

Procedure: Bronchial biopsies

Interventions

Bronchial endoscopy PROCEDURE

Bronchial endoscopy will be performed after clinical examination and pulmonary function tests

Severe Asthma

Bronchial biopsies PROCEDURE

5 biopsies will be done and analysed at the end of recruiting to assess monomeric GTP Rac1 protein expression and activity on bronchial biopsies

Controlled Sample; Mild to moderate Asthma; Severe Asthma

Bronchial alveolar enema PROCEDURE

For participants who had signed ancillary research consent

Mild to moderate Asthma; Severe Asthma

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Asthmatic Patient :
• Male or Female from 18 to 70 years old,
• Diagnosis of asthma confirmed by
• Existence of one or more following symptoms over 3 months at least (wheezing dyspnea, wheezing, chronic cough and tightness in the chest…)
• AND past pulmonary function test showing a reversible obstructive ventilatory syndrome after inhaled short-acting bronchodilators (improvement of FEV1 above 12% and at least 200 mL FEV1 gain compare to pre-bronchodilatator FEV1)
• AND a removal of the clinically suspected differential diagnoses of asthma (vocal cord dysfunction, Churg-Strauss syndrome etc…). The comorbidities should have been explored and treated or on treatment at enrollment.
• Subject agreed to participate to the study and the biological samples collection,
• Subject is affiliate to a social security system.
• Patient with one of the following criterion will be considered as severe asthmatic patient :
• Patient with a controlled asthma but using high dose of inhaled corticosteroids with another therapeutic classes,
• OR Patient with uncontrolled asthma despite treatment,
• OR Patient with worsening asthma despite treatment.
• Moderate Asthmatic patient without standard of care treatment since at least one week before the exploratory visit.
• \>Controlled sample:
• Non asthmatic cadaveric adults

You may not qualify if:

• Asthmatic Patient :
• Underage,
• Pregnant or breast-feeding women,
• Adult on guardianship
• Active smoker (smoked or Inhaled),
• former smokers (smoked or Inhaled) with a smoking history of ≥10 pack years since less than 5 years.
• Patient with asthma exacerbation the 4 past weeks before the exploratory visit..
• Patient treated by long term oral corticosteroids or ongoing biological therapy or stopped within the 3 months before exploratory visit.
• Patient with severe acute or chronic organ disorder (cardiovascular, respiratory, hepatic, renal, malabsorption)
• Patient with history of unstable angina,
• Patient with platelet count abnormality, or primary or acquired thrombopathy, or an aPTT (activated Partial Thromboplastin Time) greater than or equal to 1,5 times normal or patient with a Quick Time \> 26 seconds
• Patient under a systemic immunomodulatory or immunosuppressive treatment
• Patient with anticoagulants or anti-platelet aggregating drugs other than D-lysin acetylsalicylate and that could not be suspended before the bronchial fibroscopy.
• Patient with hypersensitivity to the treatment used during the bronchial fibroscopy: Hydroxyzine, Midazolam, Xylocaine.
• Patient with AME (Government Medical Assistance),

Sponsors & Collaborators

• Nantes University Hospital: lead
• L'institut du thorax - INSERM UMR 1087 / CNRS UMR6291 - IRS-Université de Nantes: collaborator
• IRSR-PL : Institut de Recherche en Santé Respiratoire des Pays de La Loire: collaborator

Study Sites (1)

University Hospital

Nantes, France

Location

MeSH Terms

Conditions

Asthma

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: October 30, 2017
• Study Start: March 5, 2019
• Primary Completion: November 10, 2023
• Study Completion: November 17, 2023
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)