AsthmaNaRacASNCT03325088
Assessing the Expression and the Activity of Rac1 Protein in the Airway Smooth Muscle of Asthmatic Patient
A study testing Bronchial endoscopy, Bronchial biopsies and Bronchial alveolar enema in people with Asthma, run by Nantes University Hospital at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Asthma
- What is being tested?
- Bronchial endoscopy, Bronchial biopsies and Bronchial alveolar enema
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteFrance
- Study dates
- 5 Mar 2019to 17 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- -->Inclusion criteria for non-severe asthmatic patients :
- Moderate Asthmatic patient without standard of care treatment since at least one week before the exploratory visit.
- -->Controlled sample:
- Non asthmatic cadaveric adults
Who cannot join
- 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.
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- 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),
- Patient having physical and psychological disabilities to follow the protocol,
- Patient included in another interventional research protocol,
- Patient having risk factors of Creutzfeld-Jakob disease
- Controlled sample:
- Asthmatic patient
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessing the Expression and the Activity of Rac1 Protein in the Airway Smooth Muscle of
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.
Read the detailed description
Patients will be openly labeled in one of the following group
- 15 patients with severe asthma, without oral corticosteroids treatment.,
- 6 patients with mild to moderate asthma without treatment,
- 21 controlled samples from smooth muscle cells of non-asthmatic deceased donor Bronchial endoscopy with bronchial biopsies will be assessed in all asthmatic patients, Control samples will be obtained from tracheobronchial rings of cadaveric donor. Expression and activity of Rac1 in airway smooth muscle will be determined by immuno-staining on paraffinised biopsies.
Patients will undergo two study visits (D0: inclusion visit, D15: exploratory visit) and one phone call at D21.
Inclusion Visit (D0):
- Signature of the Informed consent,
- Medical History,
- Clinical examination,
- Pulmonary Function Test,
- Blood samples for fibroscopy safety,
- ACT (Asthma Control Test), ACQ (Asthma Control Questionnaire), AQLQ (Asthma Quality of Life Questionnaire), Morisky questionnaire
Exploratory visit (D15)
- Clinical examination,
- Bronchial endoscopy with biopsies Adverse event
Phone Call (D21)
- Adverse event
Recruitment will last 4 years.
- Conditions
- Asthma
- Being tested
- Bronchial endoscopy, Bronchial biopsies, Bronchial alveolar enema
- Keywords
- Severe Asthma, airway smooth muscle cells, Rac1 protein
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchial endoscopyProcedure or surgery
Bronchial endoscopy will be performed after clinical examination and pulmonary function tests
Bronchial biopsiesProcedure or surgery
5 biopsies will be done and analysed at the end of recruiting to assess monomeric GTP Rac1 protein expression and activity on bronchial biopsies
Bronchial alveolar enemaProcedure or surgery
For participants who had signed ancillary research consent
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: Bronchial endoscopy; Procedure: Bronchial biopsies; Procedure: Bronchial alveolar enema |
| Mild to moderate Asthma | Other | patients affected with untreated mild to moderate asthma Receives: Procedure: Bronchial biopsies; Procedure: Bronchial alveolar enema |
| Controlled Sample | Other | smooth muscle cells from Tracheobronchial rings of non-asthmatic cadaveric donor Receives: Procedure: Bronchial biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Mean of fluorescence intensity of Rac1-GTP and Rac1 in paraffinised biopsies of airway smooth muscle cells.
Measured: at day 15
Assessing any correlation between Rac1-GTP/Rac1 ratio signal, pulmonary function tests and clinical data
Mean of fluorescence intensity of Rac1-GTP and Rac1 in paraffinised biopsies of airway smooth muscle cells.
Measured: at day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2017
- Study start5 Mar 2019
- Primary completion10 Nov 2023
- Study completion17 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- L'institut du thorax - INSERM UMR 1087 / CNRS UMR6291 - IRS-Université de Nantes, IRSR-PL : Institut de Recherche en Santé Respiratoire des Pays de La Loire
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03325088
- Sponsor's protocol ID
- RC16_0469
- Acronym
- NaRacAS
- Status last verified
- Apr 2024
- First submitted
- 20 Oct 2017
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Expression and the Activity of Rac1 Protein in the Airway Smooth Muscle of
- ClinicalTrials.gov ID
- NCT03325088
- Acronym / sponsor ID
- NaRacAS / RC16_0469
- Conditions
- Asthma
- Keywords
- Severe Asthma, airway smooth muscle cells, Rac1 protein
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- L'institut du thorax - INSERM UMR 1087 / CNRS UMR6291 - IRS-Université de Nantes, IRSR-PL : Institut de Recherche en Santé Respiratoire des Pays de La Loire
- Study start
- 5 Mar 2019 (actual)
- Primary completion
- 10 Nov 2023 (actual)
- Study completion
- 17 Nov 2023 (actual)
- First posted
- 30 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients will be openly labeled in one of the following group
- 15 patients with severe asthma, without oral corticosteroids treatment.,
- 6 patients with mild to moderate asthma without treatment,
- 21 controlled samples from smooth muscle cells of non-asthmatic deceased donor Bronchial endoscopy with bronchial biopsies will be assessed in all asthmatic patients, Control samples will be obtained from tracheobronchial rings of cadaveric donor. Expression and activity of Rac1 in airway smooth muscle will be determined by immuno-staining on paraffinised biopsies.
Patients will undergo two study visits (D0: inclusion visit, D15: exploratory visit) and one phone call at D21.
Inclusion Visit (D0):
- Signature of the Informed consent,
- Medical History,
- Clinical examination,
- Pulmonary Function Test,
- Blood samples for fibroscopy safety,
- ACT (Asthma Control Test), ACQ (Asthma Control Questionnaire), AQLQ (Asthma Quality of Life Questionnaire), Morisky questionnaire
Exploratory visit (D15)
- Clinical examination,
- Bronchial endoscopy with biopsies Adverse event
Phone Call (D21)
- Adverse event
Recruitment will last 4 years.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Severe Asthma | Other | Procedure: Bronchial endoscopy, Procedure: Bronchial biopsies, Procedure: Bronchial alveolar enemapatients affected with severe asthma s defined by ERS-ATS (European Respiratory Society - American Thoracic Society) without long term oral corticosteroids treatment |
| Mild to moderate Asthma | Other | Procedure: Bronchial biopsies, Procedure: Bronchial alveolar enemapatients affected with untreated mild to moderate asthma |
| Controlled Sample | Other | Procedure: Bronchial biopsiessmooth muscle cells from Tracheobronchial rings of non-asthmatic cadaveric donor |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Asthmatic Patient :
- 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.
Key exclusion criteria (20 listed)
- Asthmatic Patient :
- Controlled sample:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bronchial endoscopyBronchial endoscopy will be performed after clinical examination and pulmonary function tests | Procedure or surgery | Severe Asthma |
| Bronchial biopsies5 biopsies will be done and analysed at the end of recruiting to assess monomeric GTP Rac1 protein expression and activity on bronchial biopsies | Procedure or surgery | Controlled Sample, Mild to moderate Asthma, Severe Asthma |
| Bronchial alveolar enemaFor participants who had signed ancillary research consent | Procedure or surgery | Mild to moderate Asthma, Severe Asthma |
Primary outcome
Activity level and expression of Rac1 protein in airway smooth muscle cells of asthmatics vs non asthmatics samples
Time frame: at day 15
Mean of fluorescence intensity of Rac1-GTP and Rac1 in paraffinised biopsies of airway smooth muscle cells
2 secondary outcomes
Assessing any difference between activity level and expression of Rac1 in airway smooth muscle cells of severe versus non severe asthmatic patients.
Time frame: at day 15
Assessing any correlation between Rac1-GTP/Rac1 ratio signal, pulmonary function tests and clinical data
Time frame: at day 15
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchial endoscopy, Bronchial biopsies and Bronchial alveolar enema in people with Asthma, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activity level and expression of Rac1 protein in airway smooth muscle cells of asthmatics vs non asthmatics samples (time frame: at day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.