Paradoxical Fall in Maximum Expiratory FlowsVACUVOLNCT03062904
Search of a Paradoxical Fall in Maximum Expiratory Flow After Bronchodilation in Healthy Subjects
A study testing Inhaled Bronchodilators +/- Inhaled Methacholine in people with Paradoxical Fall in Maximum Expiratory Flows, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
There exists a physiological limitation of the expiratory flows because of the physical properties of the bronchial tree (flexible bronchial walls in a complex architecture subjected to variations of pressure and volume). Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Paradoxical Fall in Maximum Expiratory Flows
- What is being tested?
- Inhaled Bronchodilators +/- Inhaled Methacholine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2014to Dec 2019
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- All the volunteers will:
- be between 18 and 35 years/old
- be male (because of binding thoracic, more difficult to realize and more uncomfortable in the female subjects)
- have to understand French
- have to be affiliated to the social security
- have to be "non smokers, or having never smoked"
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- have to have read and have understood the information record
- have to have signed the informed consent
- have to not to be involved in a former scientific study.
- abnormal PFT (at least one value below the lower limit of normal)
- Abnormal chest radiography
- Abnormal ECG
Who cannot join
- Chronic pathology
- Long-standing treatments, recent vaccination (< 3 weeks), recent bronchitis (< 3 weeks)
- Cardio-respiratory diseases, in particular: asthma, COPD, previous pneumothorax, hemoptyses, acute coronary syndrome, uncontrolled and/or untreated cardiac arrhythmia, bradycardia (<55bpm), arterial hypertension (diastolic>95mmHg, systolic>150mmHg),
- Current abdominal disease (clinical or known hepatomegaly, irritable bowel syndrome, etc…), gastro-oesophageal reflux
- BMI < 18 and > 26
- Disorder of coagulation (and anticoagulant treatment), frequent epistaxis
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- Porphyrae
- Epilepsy, Cerebrovascular accident (stroke or transient ischemic attack) < 3 months
- Severe hepatic Insufficiency
- Glaucoma
- Benign Prostatic Hypertrophy
- Allergy: latex, lidocaine, salbutamol, ipratropium or parasympathomimetic agents
- Current allergic rhino-conjunctivitis
- History of previous oedema of Quincke or anaphylactic shock
- Aneurism of the aorta, cerebral aneurism or another arterial aneurism
- Myasthenia
- Thyroid disorders
- Protected underage child and adults
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Pitié-Salpêtrière Hospital
Paris, 75013
Eric DASQUE, Nurse, 00 33 (0) 1 42 17 85 34, eric.dasque@psl.aphp.fr
About this study
There exists a physiological limitation of the expiratory flows because of the physical properties of the bronchial tree (flexible bronchial walls in a complex architecture subjected to variations of pressure and volume). For a given lung, in a given state, for each pulmonary volume there is a corresponding Maximum Expiratory Flow (MEF). In healthy subject, the bronchial smooth muscles have a basal tonicity which is not negligible. If the tonicity is increased, this generally leads to a reduction in MEF. If it is decreased, MEF rather tends to increase, there are healthy individuals for whom the inhibition of the contraction of the bronchial smooth muscles by inhalation of bronchodilatator leads to a reduction in the MEF: this is called "paradoxical effect". When this reduction exists, it appears it occurs at low pulmonary volumes (approximately 50% for a volume of less than 25% of the CV). Under this circumstance, it seems that the basal tonicity of the bronchial smooth muscles would fight against the expiratory collapse of the bronchi, and this would happen especially for distal bronchi, for low pulmonary volume and for forceful expiration. The existence of such a phenomenon would be in favour of a "stiffening" role of the bronchial smooth muscles. The bronchial smooth muscles would not be only harmful cells causing of the asthma attacks.
Read the detailed description
There exists a physiological limitation of the expiratory flows because of the physical properties of the bronchial tree (flexible bronchial walls in a complex architecture subjected to variations of pressure and volume). For a given lung, in a given state, for each pulmonary volume there is a corresponding Maximum Expiratory Flow (MEF). In healthy subject, the bronchial smooth muscles have a basal tonicity which is not negligible. If the tonicity is increased, this generally leads to a reduction in MEF. If it is decreased, MEF rather tends to increase, there are healthy individuals for whom the inhibition of the contraction of the bronchial smooth muscles by inhalation of bronchodilatator leads to a reduction in the MEF: this is called "paradoxical effect". When this reduction exists, it appears it occurs at low pulmonary volumes (approximately 50% for a volume of less than 25% of the CV). Under this circumstance, it seems that the basal tonicity of the bronchial smooth muscles would fight against the expiratory collapse of the bronchi, and this would happen especially for distal bronchi, for low pulmonary volume and for forceful expiration. The existence of such a phenomenon would be in favour of a "stiffening" role of the bronchial smooth muscles. The bronchial smooth muscles would not be only harmful cells causing of the asthma attacks.
Primary end-point:
The aim of this study is to evaluate the occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume) after bronchodilation in certain healthy men breathing at low pulmonary volumes (by applying a chest wall strapping).
Secondary end-point:
The secondary objectives are
- to evaluate the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the following criteria/variables:
- the closing volume: we would expect an increase of it.
- modifications of forced flow-volume loop; we would expect a reduction in the MEF at low lung volumes.
- some modifications of the Pulmonary Function Test (PFT); we would expect an absence of significant difference in certain pulmonary volumes (Vital Capacity - VC, Total Lung Capacity -TLC,…), perhaps with a reduction in the Inspiratory Capacity (IC), an increase in airways resistances by high frequency oscillation
- Validation of the digital model of expiration of Florens-Filoche: towards a tool of assistance to the interpretation of the PFT.
During the various experimental sessions, we will record a certain "number" of variables that will be necessary to "feed" the final model of Florens-Filoche, such as:
- Oesophageal Pressure, Mouth Pressure: continuously. Static oesophageal pressure at:
- Residual Volume -RV, TLC, VC
- flows and pulmonary volumes continuously.
This study will attempt to develop a tool to assist in the interpretation of the PFT:
- earlier disease detection (of the bronchial smooth muscles),
- better follow-up of obstructive pathologies, their response to the treatment,
- simplification of the diagnosis of asthma,
- automation of interpretation…
Study Design:
The study includes 3 visits, as follows:
Visit 0:
Anthropometric characteristics Medical screening and eligibility criteria Chest X-ray ECG Blood pressure Pulse oximetry, heart rate PFT
Visit 1:
The first visit (V1) will last 3h and 30 minutes roughly and will consist of:
- PFT: spirometry, maximal flow-volume loops (MFVL), in sitting position.
- Closing Volume and airways resistances in sitting position.
- Insertion of a small oesophageal catheter for continuous monitoring of the oesophageal pressure and measurement of static pressure at some volumes
- Thoraco-abdominal (chest wall) strapping
- Measures of slow VC and MFVL in lying position
- Either NEP in lying position or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
- Removal of the thoraco-abdominal (chest wall) strapping
- Test of Bronchodilatation (combined Salbutamol 200μg and Ipratropium bromure 80μg; 2 inhalations): wait 30 min and then
- Thoraco-abdominal (chest wall) strapping
- Either NEP or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
- Measures of slow VC and MFVL in lying position
- Removal of the thoraco-abdominal (chest wall) strapping
- Measures of slow VC and MFVL in sitting position
- Removal of the small oesophageal catheter
- Closing Volume and airways resistances in sitting position
Each measurement will be repeated at least 3 times, until at least 2 reproducible measurements are obtained.
Visit 2:
The second meeting (V2) will be proposed only to participants who will present with a reduction in some of their MEF at the time of V1 of the protocol. It will consist of Methacholine Challenge Test. The duration of this test is approximately 1 hour.
Number of Subjects to be included: 65 healthy subjects under 35y are necessary find at lest 6 subjects presenting with a "paradoxal effect".
Duration of the study: two years
- Being tested
- Inhaled Bronchodilators +/- Inhaled Methacholine
- Keywords
- healthy, respiratory system, ventilation, paradoxical effect, methacholine, bronchodilator, NEP, EFL
- Medical subject headings
- Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Bronchodilators +/- Inhaled MethacholineDrug
- Combined Salbutamol 200μg and Ipratropium bromure 80μg (2 inhalations) if paradoxal answer
- Inhaled Methacholine based on international recommendations
| Study group | Role | What they receive |
|---|---|---|
| drug | Experimental | Not described Receives: Drug: Inhaled Bronchodilators +/- Inhaled Methacholine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
The aim of this study is to evaluate the occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume) after bronchodilation in certain healthy men breathing at low pulmonary volumes (by applying a chest wall strapping).
Measured: After bronchodilation, up to 2 hours
Secondary outcomes (3)
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the closing volume
Measured: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the modifications of forced flow-volume loop
Measured: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the inspiratory capacity airways resistances
Measured: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2017
- Study startFeb 2014
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paradoxical Fall in Maximum Expiratory FlowsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierantonio Laveneziana, MCUPH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03062904
- Sponsor's protocol ID
- P120301
- Other IDs
- 2012-A01643-40
- Acronym
- VACUVOL
- Status last verified
- Oct 2017
- First submitted
- 10 Jan 2017
- Last updated
- 17 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Search of a Paradoxical Fall in Maximum Expiratory Flow After Bronchodilation in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03062904
- Acronym / sponsor ID
- VACUVOL / P120301
- Keywords
- healthy, respiratory system, ventilation, paradoxical effect, methacholine, bronchodilator, NEP, EFL
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 24 Feb 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.
There exists a physiological limitation of the expiratory flows because of the physical properties of the bronchial tree (flexible bronchial walls in a complex architecture subjected to variations of pressure and volume). For a given lung, in a given state, for each pulmonary volume there is a corresponding Maximum Expiratory Flow (MEF). In healthy subject, the bronchial smooth muscles have a basal tonicity which is not negligible. If the tonicity is increased, this generally leads to a reduction in MEF. If it is decreased, MEF rather tends to increase, there are healthy individuals for whom the inhibition of the contraction of the bronchial smooth muscles by inhalation of bronchodilatator leads to a reduction in the MEF: this is called "paradoxical effect". When this reduction exists, it appears it occurs at low pulmonary volumes (approximately 50% for a volume of less than 25% of the CV). Under this circumstance, it seems that the basal tonicity of the bronchial smooth muscles would fight against the expiratory collapse of the bronchi, and this would happen especially for distal bronchi, for low pulmonary volume and for forceful expiration. The existence of such a phenomenon would be in favour of a "stiffening" role of the bronchial smooth muscles. The bronchial smooth muscles would not be only harmful cells causing of the asthma attacks.
Detailed description
There exists a physiological limitation of the expiratory flows because of the physical properties of the bronchial tree (flexible bronchial walls in a complex architecture subjected to variations of pressure and volume). For a given lung, in a given state, for each pulmonary volume there is a corresponding Maximum Expiratory Flow (MEF). In healthy subject, the bronchial smooth muscles have a basal tonicity which is not negligible. If the tonicity is increased, this generally leads to a reduction in MEF. If it is decreased, MEF rather tends to increase, there are healthy individuals for whom the inhibition of the contraction of the bronchial smooth muscles by inhalation of bronchodilatator leads to a reduction in the MEF: this is called "paradoxical effect". When this reduction exists, it appears it occurs at low pulmonary volumes (approximately 50% for a volume of less than 25% of the CV). Under this circumstance, it seems that the basal tonicity of the bronchial smooth muscles would fight against the expiratory collapse of the bronchi, and this would happen especially for distal bronchi, for low pulmonary volume and for forceful expiration. The existence of such a phenomenon would be in favour of a "stiffening" role of the bronchial smooth muscles. The bronchial smooth muscles would not be only harmful cells causing of the asthma attacks.
Primary end-point:
The aim of this study is to evaluate the occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume) after bronchodilation in certain healthy men breathing at low pulmonary volumes (by applying a chest wall strapping).
Secondary end-point:
The secondary objectives are
- to evaluate the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the following criteria/variables:
- the closing volume: we would expect an increase of it.
- modifications of forced flow-volume loop; we would expect a reduction in the MEF at low lung volumes.
- some modifications of the Pulmonary Function Test (PFT); we would expect an absence of significant difference in certain pulmonary volumes (Vital Capacity - VC, Total Lung Capacity -TLC,…), perhaps with a reduction in the Inspiratory Capacity (IC), an increase in airways resistances by high frequency oscillation
- Validation of the digital model of expiration of Florens-Filoche: towards a tool of assistance to the interpretation of the PFT.
During the various experimental sessions, we will record a certain "number" of variables that will be necessary to "feed" the final model of Florens-Filoche, such as:
- Oesophageal Pressure, Mouth Pressure: continuously. Static oesophageal pressure at:
- Residual Volume -RV, TLC, VC
- flows and pulmonary volumes continuously.
This study will attempt to develop a tool to assist in the interpretation of the PFT:
- earlier disease detection (of the bronchial smooth muscles),
- better follow-up of obstructive pathologies, their response to the treatment,
- simplification of the diagnosis of asthma,
- automation of interpretation…
Study Design:
The study includes 3 visits, as follows:
Visit 0:
Anthropometric characteristics Medical screening and eligibility criteria Chest X-ray ECG Blood pressure Pulse oximetry, heart rate PFT
Visit 1:
The first visit (V1) will last 3h and 30 minutes roughly and will consist of:
- PFT: spirometry, maximal flow-volume loops (MFVL), in sitting position.
- Closing Volume and airways resistances in sitting position.
- Insertion of a small oesophageal catheter for continuous monitoring of the oesophageal pressure and measurement of static pressure at some volumes
- Thoraco-abdominal (chest wall) strapping
- Measures of slow VC and MFVL in lying position
- Either NEP in lying position or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
- Removal of the thoraco-abdominal (chest wall) strapping
- Test of Bronchodilatation (combined Salbutamol 200μg and Ipratropium bromure 80μg; 2 inhalations): wait 30 min and then
- Thoraco-abdominal (chest wall) strapping
- Either NEP or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
- Measures of slow VC and MFVL in lying position
- Removal of the thoraco-abdominal (chest wall) strapping
- Measures of slow VC and MFVL in sitting position
- Removal of the small oesophageal catheter
- Closing Volume and airways resistances in sitting position
Each measurement will be repeated at least 3 times, until at least 2 reproducible measurements are obtained.
Visit 2:
The second meeting (V2) will be proposed only to participants who will present with a reduction in some of their MEF at the time of V1 of the protocol. It will consist of Methacholine Challenge Test. The duration of this test is approximately 1 hour.
Number of Subjects to be included: 65 healthy subjects under 35y are necessary find at lest 6 subjects presenting with a "paradoxal effect".
Duration of the study: two years
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| drug | Experimental | Drug: Inhaled Bronchodilators +/- Inhaled Methacholine |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- be between 18 and 35 years/old
- be male (because of binding thoracic, more difficult to realize and more uncomfortable in the female subjects)
- have to understand French
- have to be affiliated to the social security
- have to be "non smokers, or having never smoked"
Key exclusion criteria (18 listed)
- Chronic pathology
- Long-standing treatments, recent vaccination (< 3 weeks), recent bronchitis (< 3 weeks)
- Cardio-respiratory diseases, in particular: asthma, COPD, previous pneumothorax, hemoptyses, acute coronary syndrome, uncontrolled and/or untreated cardiac arrhythmia, bradycardia (<55bpm), arterial hypertension (diastolic>95mmHg, systolic>150mmHg),
- Current abdominal disease (clinical or known hepatomegaly, irritable bowel syndrome, etc…), gastro-oesophageal reflux
- BMI < 18 and > 26
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 |
|---|---|---|
| Inhaled Bronchodilators +/- Inhaled Methacholine1. Combined Salbutamol 200μg and Ipratropium bromure 80μg (2 inhalations) if paradoxal answer 2. Inhaled Methacholine based on international recommendations | Drug | drug |
Primary outcome
Occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume)
Time frame: After bronchodilation, up to 2 hours
The aim of this study is to evaluate the occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume) after bronchodilation in certain healthy men breathing at low pulmonary volumes (by applying a chest wall strapping).
3 secondary outcomes
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the closing volume
Time frame: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the modifications of forced flow-volume loop
Time frame: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Evaluation of the effect of the fall of the tonicity of the bronchial smooth muscles (normal and constrained pulmonary volumes) on the inspiratory capacity airways resistances
Time frame: after bronchodilation while breathing at low pulmonary volumes (by applying a chest wall strapping), up to 2 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
- Individual participant dataSharing planned: No
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.
Pierantonio Laveneziana, MCUPH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inhaled Bronchodilators +/- Inhaled Methacholine in people with Paradoxical Fall in Maximum Expiratory Flows, run by Assistance Publique - Hôpitaux de Paris 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 12 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 17 May 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pierantonio Laveneziana, MCUPH (00 33 (0) 1 42 17 85 84, pierantonio.laveneziana@psl.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence or increase of the Expiratory Flow Limitation (EFL) under either Negative Expiratory Pressure (NEP) or submaximal gentle forced expiratory manoeuvres (partial flow-volume loops at tidal volume) (time frame: After bronchodilation, up to 2 hours). 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 17 May 2018.