Pulmonary Disease, Chronic ObstructiveINVECCONCT03181204
Modeling Bronchial Epithelium Modifications Associated With COPD Using iPS
An observational study of Pulmonary Disease, Chronic Obstructive and Smoking, run by University Hospital, Montpellier at 1 site in France.
Trial summary
The primary objective of this study is to to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments: Differentiation of an Induced Pluripotent Stem cell (iPS) clone derived from cutaneous biopsy in a population of heavy smokers (plus patients with chronic… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, Smoking
- What is being tested?
- Bronchial biopsy, Skin biopsy and Blood sample
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- 7 Aug 2017to 9 Mar 2022
- Phase
- Observational
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: This study includes patients with chronic obstructive pulmonary disease, as well as patients without chronic obstructive pulmonary disease, but who are heavy smokers.
Who may be able to join
- The patient has given his/her signed, informed consent
- Forced expiratory volume in 1 second / forced vital capacity < 0.7 [FEV1/FVC < 0.7]
- FEV1 < 50% of predicted value
- Exclusion of other respiratory pathologies, based on anamnesis, computed tomography and complementary respiratory function tests and transthoracic ultrasound,
- Smoking >10 pack-years, ongoing or weaned
- Absence of exacerbation or intercurrent infectious episode for at least 4 weeks at time of inclusion
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- Medical indication for a bronchial fibroscopy (indication validated by the physician in charge of the patient and the study investigating physician): pulmonary peripheral nodule exploration with computed tomography, interventional endoscopy for emphysema reduction, removal of foreign bodies, other indications.
- Absence of contraindications for bronchial biopsy (left to physician's discretion): not limited to: regular intake of anticoagulants or anti-platelet aggregation, hemostasis abnormalities
- The patient has given his/her signed, informed consent
- Forced expiratory volume in 1 second / forced vital capacity > 0.7 [FEV1/FVC > 0.7]
- FEV1 > 80% of predicted value
- Exclusion of other respiratory pathologies, based on anamnesis, computed tomography (absence of extensive emphysema lesions defined by the presence of less than <5% relative surface area occupied by densities less than 910 UH (measured on millimeter cuts)) and respiratory function tests (Residual Volume <120%, Diffusion Capacity for Carbon Monoxide > 60% and Total Pulmonary Capacity> 120%) and transthoracic ultrasound (normal),
- Smoking >40 pack-years, ongoing or weaned
- Absence of exacerbation or intercurrent infectious episode for at least 4 weeks at time of inclusion
- Medical indication for a bronchial fibroscopy (indication validated by the physician in charge of the patient and the study investigating physician): pulmonary peripheral nodule exploration with computed tomography, interventional endoscopy for emphysema reduction, removal of foreign bodies, other indications.
- Absence of contraindications for bronchial biopsy (left to physician's discretion): not limited to: regular intake of anticoagulants or anti-platelet aggregation, hemostasis abnormalities
Who cannot join
- Contra-indication for bronchial fibroscopy and cutaneous biopsy
- Deficiency in α-1 antitrypsin
- Significant bronchiectasis on chest computed tomography scan
- Colonization of the airways by Pseudomonas Aeroginosa or Aspergillus
- Chemotherapy or other cytotoxic treatments in the last 12 months
- Systemic corticotherapy in the 4 weeks prior to inclusion
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- Long-term antibiotic treatment, notably by macrolides
- Any other treatment that may affect the bronchial epithelium, this being left to the discretion of the investigating physician
- Consumer of illicit drugs or alcohol
- Participant in an exclusion period determined by a previous study
- Subject not affiliated with, or not beneficiary of, a social security plan.
- Pregnant or nursing women according to Article L1121-5 of the Public Health Code.
- Vulnerable persons according to Article L1121-6 of the Public Health Code
- An adult who is protected or incapable of giving consent in accordance with Article L1121-8 of the Public Health Code
- Subject deprived of freedom by judicial or administrative decision.
- Those patients for whom two epithelia cultures (1 from bronchial biopsy ("ALI") and 1 from fibroblast reprogrammation of redifferentiated iPS ("iALI")) were not obtained will be excluded (post-inclusion).
Trial locations and contacts
1 site in 1 country.
France1 site
Centre Hospitalier Universitaire de Montpellier
Montpellier, 34295
About this study
Official title: Modeling Bronchial Epithelia Modifications Associated With Chronic Obstructive Pulmonary Disease (COPD) Using Induced Pluripotent Stemcells (iPS)
The primary objective of this study is to to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:
- Differentiation of an Induced Pluripotent Stem cell (iPS) clone derived from cutaneous biopsy in a population of heavy smokers (plus patients with chronic obstructive pulmonary disease) in order to obtain differentiated bronchial epithelia in vitro.
- For each of these same patients, generation of bronchial epithelium in vitro from bronchial biopsy using human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures.
Read the detailed description
Secondary objectives:
- Confrontation of the two models of in vitro generation of bronchial epithelium by iPS and ALI in order to validate our model of study of the human bronchial epithelium COPD generated by the iPS.
- Inducing a "COPD-like" epithelial phenotype by exposing the bronchial epithelia generated from the iPS to a source of in vitro toxin (tobacco) and studying its effects by transcriptomic analysis via high-throughput sequencing (NGS) at key steps during the model.
- Demonstrate the feasibility of obtaining iPS from peripheral blood sampling.
- Conditions
- Pulmonary Disease, Chronic Obstructive, Smoking
- Being tested
- Bronchial biopsy, Skin biopsy, Blood sample
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchial biopsyProcedure or surgery
The bronchial biopsy is part of this study's inclusion criteria and is required during routine care for the patient. Bronchial fibroscopy is performed under general or local anesthesia. Biopsies are performed using forceps and according to current recommendations. One biopsy will be fixed immediately in RCL2 medium while the others (between 3 and 6) will be kept in isotonic saline and rapidly prepared for air-liquid-interface (ALI) cell culture.
Skin biopsyProcedure or surgery
The skin biopsy will be performed after local anesthesia by hypodermic injection of a 1% Xylocaine solution. A single sample of a skin fragment about 3 mm in diameter will be necessary.
Blood sampleProcedure or surgery
The blood sample will be taken at the end of the cutaneous biospy, approximately 20 ml of blood will be collected.
| Study group | Role | What they receive |
|---|---|---|
| Patients likely to develop COPD | Patients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD).
Intervention: Bronchial biopsy
Intervention: Skin biopsy
Intervention: Blood sample Receives: Procedure: Bronchial biopsy; Procedure: Skin biopsy; Procedure: Blood sample | |
| Patients not likely to develop COPD | Patients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD).
Intervention: Bronchial biopsy
Intervention: Skin biopsy
Intervention: Blood sample Receives: Procedure: Bronchial biopsy; Procedure: Skin biopsy; Procedure: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
functional bronchial epithelium from iPS?
Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood or fibroblasts? (yes/no)
Measured: Day 0 + culture (cross-sectional study)
functional bronchial epithelium from HBEC-ALI?
Was a functional bronchial epithelium obtained from the patient's bronchial biopsy: human bronchial epithelial cell culture on an air-liquid-interface? (yes/no)
Measured: Day 0 + culture (cross-sectional study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2017
- Study start7 Aug 2017
- Primary completion9 Mar 2022
- Study completion9 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Arnaud Bourdin, MD, PhD, Study director, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03181204
- Sponsor's protocol ID
- 9791
- Other IDs
- 2017-A00252-51
- Acronym
- INVECCO
- Status last verified
- Sep 2023
- First submitted
- 6 Jun 2017
- Last updated
- 8 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ahmed E, Fieldes M, Mianne J, Bourguignon C, Nasri A, Vachier I, Assou S, Bourdin A, De Vos J. Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells. Stem Cell Res. 2021 Oct;56:102550. doi: 10.1016/j.scr.2021.102550. Epub 2021 Sep 27.
PubMed 34624616Fieldes M, Ahmed E, Bourguignon C, Mianne J, Vernisse C, Fort A, Vachier I, Bourdin A, Assou S, De Vos J. [Modelling the bronchial epithelium in chronic obstructive pulmonary disease using human induced pluripotential stem cells]. Rev Mal Respir. 2020 Mar;37(3):197-200. doi: 10.1016/j.rmr.2020.02.003. Epub 2020 Mar 4. French.
PubMed 32146059
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modeling Bronchial Epithelia Modifications Associated With Chronic Obstructive Pulmonary Disease (COPD) Using Induced Pluripotent Stemcells (iPS)
- ClinicalTrials.gov ID
- NCT03181204
- Acronym / sponsor ID
- INVECCO / 9791
- Conditions
- Pulmonary Disease, Chronic Obstructive, Smoking
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 8 Jun 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.
The primary objective of this study is to to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:
- Differentiation of an Induced Pluripotent Stem cell (iPS) clone derived from cutaneous biopsy in a population of heavy smokers (plus patients with chronic obstructive pulmonary disease) in order to obtain differentiated bronchial epithelia in vitro.
- For each of these same patients, generation of bronchial epithelium in vitro from bronchial biopsy using human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures.
Detailed description
Secondary objectives:
- Confrontation of the two models of in vitro generation of bronchial epithelium by iPS and ALI in order to validate our model of study of the human bronchial epithelium COPD generated by the iPS.
- Inducing a "COPD-like" epithelial phenotype by exposing the bronchial epithelia generated from the iPS to a source of in vitro toxin (tobacco) and studying its effects by transcriptomic analysis via high-throughput sequencing (NGS) at key steps during the model.
- Demonstrate the feasibility of obtaining iPS from peripheral blood sampling.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients likely to develop COPD | – | Procedure: Bronchial biopsy, Procedure: Skin biopsy, Procedure: Blood samplePatients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample |
| Patients not likely to develop COPD | – | Procedure: Bronchial biopsy, Procedure: Skin biopsy, Procedure: Blood samplePatients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- This study includes patients with chronic obstructive pulmonary disease, as well as patients without chronic obstructive pulmonary disease, but who are heavy smokers.
Key inclusion criteria (16 listed)
- The patient has given his/her signed, informed consent
- Forced expiratory volume in 1 second / forced vital capacity < 0.7 [FEV1/FVC < 0.7]
- FEV1 < 50% of predicted value
- Exclusion of other respiratory pathologies, based on anamnesis, computed tomography and complementary respiratory function tests and transthoracic ultrasound,
- Smoking >10 pack-years, ongoing or weaned
Key exclusion criteria (16 listed)
- Contra-indication for bronchial fibroscopy and cutaneous biopsy
- Deficiency in α-1 antitrypsin
- Significant bronchiectasis on chest computed tomography scan
- Colonization of the airways by Pseudomonas Aeroginosa or Aspergillus
- Chemotherapy or other cytotoxic treatments in the last 12 months
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 biopsyThe bronchial biopsy is part of this study's inclusion criteria and is required during routine care for the patient. Bronchial fibroscopy is performed under general or local anesthesia. Biopsies are performed using forceps and according to current recommendations. One biopsy will be fixed immediately in RCL2 medium while the others (between 3 and 6) will be kept in isotonic saline and rapidly prepared for air-liquid-interface (ALI) cell culture. | Procedure or surgery | Patients likely to develop COPD, Patients not likely to develop COPD |
| Skin biopsyThe skin biopsy will be performed after local anesthesia by hypodermic injection of a 1% Xylocaine solution. A single sample of a skin fragment about 3 mm in diameter will be necessary. | Procedure or surgery | Patients likely to develop COPD, Patients not likely to develop COPD |
| Blood sampleThe blood sample will be taken at the end of the cutaneous biospy, approximately 20 ml of blood will be collected. | Procedure or surgery | Patients likely to develop COPD, Patients not likely to develop COPD |
Primary outcome
functional bronchial epithelium from iPS?
Time frame: Day 0 + culture (cross-sectional study)
Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood or fibroblasts? (yes/no)
functional bronchial epithelium from HBEC-ALI?
Time frame: Day 0 + culture (cross-sectional study)
Was a functional bronchial epithelium obtained from the patient's bronchial biopsy: human bronchial epithelial cell culture on an air-liquid-interface? (yes/no)
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 8 Sep 2023.
- Results publication: PubMed 34624616Ahmed E, Fieldes M, Mianne J, Bourguignon C, Nasri A, Vachier I, Assou S, Bourdin A, De Vos J. Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells. Stem Cell Res. 2021 Oct;56:102550. doi: 10.1016/j.scr.2021.102550. Epub 2021 Sep 27.
- Results publication: PubMed 32146059Fieldes M, Ahmed E, Bourguignon C, Mianne J, Vernisse C, Fort A, Vachier I, Bourdin A, Assou S, De Vos J. [Modelling the bronchial epithelium in chronic obstructive pulmonary disease using human induced pluripotential stem cells]. Rev Mal Respir. 2020 Mar;37(3):197-200. doi: 10.1016/j.rmr.2020.02.003. Epub 2020 Mar 4. French.
- INVECCO on the Open Science FrameworkLink provided by the sponsor.
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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.
Arnaud Bourdin, MD, PhD study director
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Disease, Chronic Obstructive and Smoking, run by University Hospital, Montpellier 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 16 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 8 Sep 2023. 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?
functional bronchial epithelium from iPS? (time frame: Day 0 + culture (cross-sectional study)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03181204, which also lists 2 linked publications.
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 8 Sep 2023; AzTrials last refreshed its copy on 30 Oct 2026.