Chronic Obstructive Pulmonary Disease SeverePhase 2/3CEL&VALNCT04018729
Cell Therapy Associated With Endobronchial Valve
A Phase 2/3 study testing Zephyr Endobronchial Valve and Marrow-derived mesenchymal stromal cell in people with Chronic Obstructive Pulmonary Disease Severe, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial summary
Chronic obstructive pulmonary disease (COPD) is one of the most common diseases worldwide and is considered a public health problem. The World Health Organization estimates that about 210 million people have COPD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease Severe
- What is being tested?
- Zephyr Endobronchial Valve and Marrow-derived mesenchymal stromal cell
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteBrazil
- Study dates
- 19 Nov 2019to 30 Apr 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of severe heterogeneous pulmonary emphysema (at least 10% of total lung parenchyma or 25% of target lobe with density < -950HU);
- Heterogeneity> 15pp (difference of at least 15 percentage points of lung parenchyma with density greater than -950HU between the treated lobe(s) and the remaining lung on the same side)
- Estimates of low or non-existent collateral ventilation (fissure integrity> 95% measured by VIDA Diagnostics or collateral ventilation measured by negative Chartis® System)
- Total lung capacity> 100% of predicted
- Residual volume> 175% of predicted
- FEV1 <50% of predicted post-bronchodilator
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- DLCO (diffusing capacity of the lungs for carbon monoxide) <45% of predicted post-bronchodilator
- Body Mass Index (BMI) Greater than 18Kg/m2 and less than 35Kg/m2.
- Optimized clinical treatment
- Daily physical activities limitation
- Possibility of pulmonary rehabilitation
- Preserved ventricular function (LVEF> 40%)
- Cessation of smoking ≥ 4 months
- Dyspnea MMRC ≥ 2
Who cannot join
- Homogeneous emphysema
- Estimated collateral ventilation observed on CT scanned by VIDA vision software (VIDA vision®, VIDA Diagnostics, Iowa-USA) - Fissure integrity on target lobe less than 75%.
- Use of continuous systemic corticosteroid therapy> 20mg QD (quaque die, once a day) of prednisone (or equivalent)
- Active lung or extra pulmonary infection
- Coronary heart disease and/or severe ventricular dysfunction
- Significant renal or hepatic disease
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- Immunosuppressive disease
- Rheumatologic or orthopedic disease limiting physical capacity;
- Cognitive inability to understand study procedures;
- Impression by clinical research investigators with a lifespan of less than a year1;
- Active smoking
- Malignant neoplasia with estimated prognosis of survival <2 years
- Psychosocial problems
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035903
Hugo G Oliveira, PhD, 55 51 3359-1337, holiveira@hcpa.edu.br
Igor G Benedetto, MSc, 55 51 3359-1337, ibenedetto@hcpa.edu.br
About this study
Official title: Bone Marrow-Derived Mesenchymal Stromal Cell Therapy Associated With Unidirectional Endobronchial Valve in Patients With Severe Pulmonary Emphysema: A Randomized Clinical Trial
Chronic obstructive pulmonary disease (COPD) is one of the most common diseases worldwide and is considered a public health problem. The World Health Organization estimates that about 210 million people have COPD. Disease-related mortality is more than 3 million, representing 5% of all deaths, 90% of this mortality being concentrated in middle- and low-income countries. COPD can be subdivided into chronic bronchitis and emphysema. Emphysema, the focus of this project, is histologically defined by the permanent increase of the distal air spaces to the terminal bronchioles associated with the destruction of the alveolar septa in the lung. Approximately two-thirds of adult men and a quarter of women (most without dysfunction) will have well-defined emphysema, but often of limited extent.
Mesenchymal stem cells (MSCs) have anti-inflammatory, anti-fibrotic, microbicide and repair potential. Regarding COPD, several authors have concentrated efforts in the investigation of the relationship between the severity of the condition and the various sources of adult stem cells. Apparently the lungs have a high chemotactic effect in relation to adult stem cells, since several studies have evidenced a high implantation (6-20%) of stem cells derived from bone marrow, administered systemically, in the pulmonary tissue of receptors. Therefore, MSCs has been tested in different lung diseases have no effective treatment, such as pulmonary fibrosis, acute respiratory distress syndrome, asthma, COPD positive results, such as reduction of fibrosis, reduction of proliferation inflammatory cells and cytokines, reduction of infectious processes and recovery of the histological changes caused by pulmonary emphysema.
Based on these findings, the purpose of this project is to evaluate the safety and efficacy of endoscopic administration of bone marrow stem cells in patients with severe homogeneous emphysema and evaluating the feasibility, efficacy and safety of this procedure.
- Being tested
- Zephyr Endobronchial Valve, Marrow-derived mesenchymal stromal cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zephyr Endobronchial ValveDevice
Endoscopic lung volume reduction therapy.
Marrow-derived mesenchymal stromal cellBiological
Mesenchymal stem cells have anti-inflammatory, anti-fibrotic, microbicide and repair potential.
| Study group | Role | What they receive |
|---|---|---|
| Endobronchial valve + marrow-derived mesenchymal stromal cell | Experimental | Not described Receives: Device: Zephyr Endobronchial Valve; Biological: Marrow-derived mesenchymal stromal cell |
| Endobronchial valve | Active comparator | Not described Receives: Device: Zephyr Endobronchial Valve |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause death
Expressed as the total number of death due to all conditions during the clinical trial.
Measured: 6 months
Number of participants with worsening of dyspnea
Number of participants with worsening of dyspnea as measured by the mMRC-Modified Medical Research Council (1 point increase in the measured scale). The mMRC Dyspnea Scale quantifies disability attributable to breathlessness (range from 1-4), and is useful for characterizing baseline dyspnea in patients with respiratory diseases.
Measured: 6 months
Number of participants with respiratory functional worsening
Number of participants with respiratory functional worsening as measured by decrease of 15% or more in FEV1 (forced expiratory volume in one second). FEV1 is a measurement taken from a pulmonary function test. It calculates the amount of air that a person can force out of their lungs in 1 second.
Measured: 6 months
Impairment of exercise capacity
Impairment of exercise capacity as measured by reduction of 35 m in the 6-minute walk test. The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The test provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
Measured: 6 months
Increased oxygen use
Outcome measure result: number of participants with 1 point increase in oxygen need as classification on the chart above 0 - no oxygen use 1- intermittent use <6h/day 2- intermittent use >6h/dia 3 - continuous oxygen use
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start19 Nov 2019
- Primary completion17 Aug 2020
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary Disease SevereStudies 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Pontifícia Universidade Católica do Paraná, Universidade Federal do Rio de Janeiro
- Responsible party
- Sponsor
- Investigators
- Hugo G Oliveira, PhD, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04018729
- Sponsor's protocol ID
- 2018-0327
- Acronym
- CEL&VAL
- Status last verified
- Dec 2022
- First submitted
- 10 May 2019
- Last updated
- 14 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Marrow-Derived Mesenchymal Stromal Cell Therapy Associated With Unidirectional Endobronchial Valve in Patients With Severe Pulmonary Emphysema: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04018729
- Acronym / sponsor ID
- CEL&VAL / 2018-0327
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Pontifícia Universidade Católica do Paraná, Universidade Federal do Rio de Janeiro
- Study start
- 19 Nov 2019 (actual)
- Primary completion
- 17 Aug 2020 (actual)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 12 Jul 2019 (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.
Chronic obstructive pulmonary disease (COPD) is one of the most common diseases worldwide and is considered a public health problem. The World Health Organization estimates that about 210 million people have COPD. Disease-related mortality is more than 3 million, representing 5% of all deaths, 90% of this mortality being concentrated in middle- and low-income countries. COPD can be subdivided into chronic bronchitis and emphysema. Emphysema, the focus of this project, is histologically defined by the permanent increase of the distal air spaces to the terminal bronchioles associated with the destruction of the alveolar septa in the lung. Approximately two-thirds of adult men and a quarter of women (most without dysfunction) will have well-defined emphysema, but often of limited extent.
Mesenchymal stem cells (MSCs) have anti-inflammatory, anti-fibrotic, microbicide and repair potential. Regarding COPD, several authors have concentrated efforts in the investigation of the relationship between the severity of the condition and the various sources of adult stem cells. Apparently the lungs have a high chemotactic effect in relation to adult stem cells, since several studies have evidenced a high implantation (6-20%) of stem cells derived from bone marrow, administered systemically, in the pulmonary tissue of receptors. Therefore, MSCs has been tested in different lung diseases have no effective treatment, such as pulmonary fibrosis, acute respiratory distress syndrome, asthma, COPD positive results, such as reduction of fibrosis, reduction of proliferation inflammatory cells and cytokines, reduction of infectious processes and recovery of the histological changes caused by pulmonary emphysema.
Based on these findings, the purpose of this project is to evaluate the safety and efficacy of endoscopic administration of bone marrow stem cells in patients with severe homogeneous emphysema and evaluating the feasibility, efficacy and safety of this procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endobronchial valve + marrow-derived mesenchymal stromal cell | Experimental | Device: Zephyr Endobronchial Valve, Biological: Marrow-derived mesenchymal stromal cell |
| Endobronchial valve | Active comparator | Device: Zephyr Endobronchial Valve |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Diagnosis of severe heterogeneous pulmonary emphysema (at least 10% of total lung parenchyma or 25% of target lobe with density < -950HU);
- Heterogeneity> 15pp (difference of at least 15 percentage points of lung parenchyma with density greater than -950HU between the treated lobe(s) and the remaining lung on the same side)
- Estimates of low or non-existent collateral ventilation (fissure integrity> 95% measured by VIDA Diagnostics or collateral ventilation measured by negative Chartis® System)
- Total lung capacity> 100% of predicted
- Residual volume> 175% of predicted
Key exclusion criteria (14 listed)
- Homogeneous emphysema
- Estimated collateral ventilation observed on CT scanned by VIDA vision software (VIDA vision®, VIDA Diagnostics, Iowa-USA) - Fissure integrity on target lobe less than 75%.
- Use of continuous systemic corticosteroid therapy> 20mg QD (quaque die, once a day) of prednisone (or equivalent)
- Active lung or extra pulmonary infection
- Coronary heart disease and/or severe ventricular dysfunction
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 |
|---|---|---|
| Zephyr Endobronchial ValveEndoscopic lung volume reduction therapy. | Device | Endobronchial valve, Endobronchial valve + marrow-derived mesenchymal stromal cell |
| Marrow-derived mesenchymal stromal cellMesenchymal stem cells have anti-inflammatory, anti-fibrotic, microbicide and repair potential. | Biological | Endobronchial valve + marrow-derived mesenchymal stromal cell |
Primary outcome
All-cause death
Time frame: 6 months
Expressed as the total number of death due to all conditions during the clinical trial.
Number of participants with worsening of dyspnea
Time frame: 6 months
Number of participants with worsening of dyspnea as measured by the mMRC-Modified Medical Research Council (1 point increase in the measured scale). The mMRC Dyspnea Scale quantifies disability attributable to breathlessness (range from 1-4), and is useful for characterizing baseline dyspnea in patients with respiratory diseases.
Number of participants with respiratory functional worsening
Time frame: 6 months
Number of participants with respiratory functional worsening as measured by decrease of 15% or more in FEV1 (forced expiratory volume in one second). FEV1 is a measurement taken from a pulmonary function test. It calculates the amount of air that a person can force out of their lungs in 1 second.
Impairment of exercise capacity
Time frame: 6 months
Impairment of exercise capacity as measured by reduction of 35 m in the 6-minute walk test. The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The test provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
Increased oxygen use
Time frame: 6 months
Outcome measure result: number of participants with 1 point increase in oxygen need as classification on the chart above 0 - no oxygen use 1- intermittent use <6h/day 2- intermittent use >6h/dia 3 - continuous oxygen use
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
- 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.
Hugo G Oliveira, PhD principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Zephyr Endobronchial Valve and Marrow-derived mesenchymal stromal cell in people with Chronic Obstructive Pulmonary Disease Severe, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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 14 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 14 Dec 2022. 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 Brazil. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hugo G Oliveira, PhD (+55 51 3359-8241 ext. 8241, hugo@hugooliveira.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause death (time frame: 6 months). The study lists 5 primary outcomes in all. 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 14 Dec 2022.