Covid-19Phase 2/3NCT04366063
Mesenchymal Stem Cell Therapy for SARS-CoV-2-related Acute Respiratory Distress Syndrome
A Phase 2/3 study testing Cell therapy protocol 1 and Cell therapy protocol 2 in people with Covid-19, run by Royan Institute at 1 site in Iran.
Trial summary
Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Covid-19
- What is being tested?
- Cell therapy protocol 1 and Cell therapy protocol 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIran
- Study dates
- 5 Apr 2020to 10 Dec 2020
- Phase
- Phase 2/3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmation of 2019-nCoV infection by RT-PCR
- Diagnosis of ARDS according to the Berlin definition of ARDS
- Requiring supplemental oxygen
- Pneumonia that is judged by chest radiograph or CT
- PaO2/oxygen absorption concentration (FiO2) ≤ 300MMHG
- Pulmonary imaging shows that the focused progress > 50% in 24-48 hours
- Mild to Moderate 2019-nCoV pneumonia/ stay in the ICU <48 hours
- SOFA score between 2-3 point
Who cannot join
- Severe allergies or allergies after 1st injection to stem cell preparations and their components
- Patients with a malignant tumor, other serious systemic diseases, and psychosis
- Co-Infection of HIV, tuberculosis, influenza virus, adenovirus, and other respiratory infection viruses
- Patients with a previous history of pulmonary embolism
- Be thought by researchers to be inappropriate to participate in this clinical study (Expected deaths within 48 hours, uncontrolled infections)
- Liver or kidney SOFA score of more than 3 points; combined with other organ failures (need organ support), Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30)
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- Pulmonary obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis, allergic alveolitis, and other known viral pneumonia or bacterial pneumonia
- Continuous use of immunosuppressive agents or organ transplants in the past 6 months
- In vitro life support (ECMO, ECCO2R, RRT)
- Pregnant or lactating women
- Uncontrolled underlying disease
Trial locations and contacts
1 site in 1 country.
Iran1 site, 1 recruiting
- Recruiting
Royan Institute
Tehran, 16635148
Masoumeh Nouri, masoume.nouri2002@gmail.com
Hoda Madani, hoda62_m@yahoo.com
About this study
Official title: Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome in Coronavirus Infection: A Phase 2-3 Clinical Trial
Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed.
Read the detailed description
Acute respiratory distress syndrome (ARDS) is the major cause of death in the COVID 19 infection pandemic. It is a devastating clinical condition, caused by an acute and diffuse lung injury that requires management in the intensive care unit. It is caused by uncontrolled inflammation that leads to severe pulmonary alveolar damage and capillary membrane leakage, and progressive respiratory failure. There is no effective treatment for ARDS and the only supportive care strategies are the mainstay of therapy. Mesenchymal stem cells (MSCs) have high regenerative and immunomodulatory capacities. In preclinical research, ARDS, MSCs modulate the inflammatory response, augment tissue repair, enhance pathogen clearance, and reduce the severity of the injury, pulmonary dysfunction, and apoptosis. Moreover, many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus (e.g., Influenza)-induced lung injury and mortality in animals. Since 2014 clinical trials are using MSC from variable sources [bone marrow (BM), fat, and umbilical cord (UC)] in the treatment of ARDS. Some of the clinical trials are ongoing and the final reports are not reported. In all final reports, the safety of the application of MSC has been documented and most of them implied improvement in mortality and decrease of morbidity. Moreover, experimental studies have demonstrated that MSCs or their extracellular vesicles (MSCs-EVs) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. Also, macrophage phagocytosis, bacterial killing, and the outcome are improved. It is highly likely that MSCs-EVs have the same therapeutic effect on inoculation pneumonia as MSCs themselves.
Critically ill coronavirus documented cases suspicious to ARDS (mild or moderate) will be enrolled in the study. Our previous experiment (IRCT20200217046526N1) showed the safety of 3 injections of MSCs in patients with COVID-19. This multi-center trial will recruit 60 patients. All patients in all groups will receive conventional therapy for virus treatment and supportive care for ARDS.
The patients allocated randomly to three groups:
Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control.
Intervention Group1 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 intravenously.
Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 plus two doses of extracellular vesicles (EVs) on Day 4 and Day 6 intravenously.
The clinical symptoms, pulmonary imaging, side effects, 28-days mortality inflammatory factors, etc. will be evaluated during the 28 days follow up.
- Conditions
- Covid-19
- Being tested
- Cell therapy protocol 1, Cell therapy protocol 2
- Keywords
- COVID-19, Acute Respiratory Distress Syndrome, 2019 Novel Coronavirus Pneumonia
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cell therapy protocol 1Biological
Cell therapy protocol 1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) at Day 0 and Day 2 plus Conventional treatment.
Cell therapy protocol 2Biological
Patients will receive two doses of MSCs 100×10e6 (±10%)at Day 0 and Day 2, intravenously plus two doses of EVs at Day 4 and Day 6 plus conventional treatment.
| Study group | Role | What they receive |
|---|---|---|
| Two MSC infusion | Experimental | Intervention Group1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) intravenously plus Conventional treatment. Receives: Biological: Cell therapy protocol 1 |
| Two MSC infusion Plus two EVs infusion | Experimental | Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), intravenously plus two doses of EVs plus Conventional treatment Receives: Biological: Cell therapy protocol 2 |
| Control | No intervention | Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events assessment
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: From baseline to day 28
Blood oxygen saturation
Evaluation of Pneumonia Improvement
Measured: From baseline to day 14
Secondary outcomes (4)
Intensive care unit-free days
Number of days
Measured: Up to day 8
Clinical symptoms
Improvement of clinical symptoms including duration of fever, respiratory distress, pneumonia, cough, sneezing
Measured: From baseline to day 14
Respiratory efficacy
increase in PaO2/FiO2 ratio from baseline to day 7
Measured: From baseline to day 7
Biomarkers concentrations in plasma
Biochemical examination
Measured: At baseline, 7, 14, 28 days after the first intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2020
- Study start5 Apr 2020
- Primary completion6 Jun 2020 (estimated)
- Study completion10 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid-19Studies 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
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Collaborators
- Tehran University of Medical Sciences, Shahid Beheshti University of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Abdol Hossein Shahverdi, Study chair, Royan InstituteHossein Baharvand, Professor, Principal investigator, Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cells Biology & Technology, Iran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04366063
- Sponsor's protocol ID
- 991919
- Other IDs
- IRCT20200217046526N2
- Status last verified
- Apr 2020
- First submitted
- 20 Apr 2020
- Last updated
- 30 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome in Coronavirus Infection: A Phase 2-3 Clinical Trial
- ClinicalTrials.gov ID
- NCT04366063
- Acronym / sponsor ID
- 991919
- Conditions
- Covid-19
- Keywords
- COVID-19, Acute Respiratory Distress Syndrome, 2019 Novel Coronavirus Pneumonia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Royan InstituteOther government
- Collaborators
- Tehran University of Medical Sciences, Shahid Beheshti University of Medical Sciences
- Study start
- 5 Apr 2020 (actual)
- Primary completion
- 6 Jun 2020 (estimated)
- Study completion
- 10 Dec 2020 (estimated)
- First posted
- 28 Apr 2020 (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.
Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed.
Detailed description
Acute respiratory distress syndrome (ARDS) is the major cause of death in the COVID 19 infection pandemic. It is a devastating clinical condition, caused by an acute and diffuse lung injury that requires management in the intensive care unit. It is caused by uncontrolled inflammation that leads to severe pulmonary alveolar damage and capillary membrane leakage, and progressive respiratory failure. There is no effective treatment for ARDS and the only supportive care strategies are the mainstay of therapy. Mesenchymal stem cells (MSCs) have high regenerative and immunomodulatory capacities. In preclinical research, ARDS, MSCs modulate the inflammatory response, augment tissue repair, enhance pathogen clearance, and reduce the severity of the injury, pulmonary dysfunction, and apoptosis. Moreover, many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus (e.g., Influenza)-induced lung injury and mortality in animals. Since 2014 clinical trials are using MSC from variable sources [bone marrow (BM), fat, and umbilical cord (UC)] in the treatment of ARDS. Some of the clinical trials are ongoing and the final reports are not reported. In all final reports, the safety of the application of MSC has been documented and most of them implied improvement in mortality and decrease of morbidity. Moreover, experimental studies have demonstrated that MSCs or their extracellular vesicles (MSCs-EVs) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. Also, macrophage phagocytosis, bacterial killing, and the outcome are improved. It is highly likely that MSCs-EVs have the same therapeutic effect on inoculation pneumonia as MSCs themselves.
Critically ill coronavirus documented cases suspicious to ARDS (mild or moderate) will be enrolled in the study. Our previous experiment (IRCT20200217046526N1) showed the safety of 3 injections of MSCs in patients with COVID-19. This multi-center trial will recruit 60 patients. All patients in all groups will receive conventional therapy for virus treatment and supportive care for ARDS.
The patients allocated randomly to three groups:
Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control.
Intervention Group1 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 intravenously.
Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 plus two doses of extracellular vesicles (EVs) on Day 4 and Day 6 intravenously.
The clinical symptoms, pulmonary imaging, side effects, 28-days mortality inflammatory factors, etc. will be evaluated during the 28 days follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Two MSC infusion | Experimental | Biological: Cell therapy protocol 1Intervention Group1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) intravenously plus Conventional treatment. |
| Two MSC infusion Plus two EVs infusion | Experimental | Biological: Cell therapy protocol 2Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), intravenously plus two doses of EVs plus Conventional treatment |
| Control | No intervention | –Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmation of 2019-nCoV infection by RT-PCR
- Diagnosis of ARDS according to the Berlin definition of ARDS
- Requiring supplemental oxygen
- Pneumonia that is judged by chest radiograph or CT
- PaO2/oxygen absorption concentration (FiO2) ≤ 300MMHG
Key exclusion criteria (11 listed)
- Severe allergies or allergies after 1st injection to stem cell preparations and their components
- Patients with a malignant tumor, other serious systemic diseases, and psychosis
- Co-Infection of HIV, tuberculosis, influenza virus, adenovirus, and other respiratory infection viruses
- Patients with a previous history of pulmonary embolism
- Be thought by researchers to be inappropriate to participate in this clinical study (Expected deaths within 48 hours, uncontrolled infections)
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 |
|---|---|---|
| Cell therapy protocol 1Cell therapy protocol 1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) at Day 0 and Day 2 plus Conventional treatment. | Biological | Two MSC infusion |
| Cell therapy protocol 2Patients will receive two doses of MSCs 100×10e6 (±10%)at Day 0 and Day 2, intravenously plus two doses of EVs at Day 4 and Day 6 plus conventional treatment. | Biological | Two MSC infusion Plus two EVs infusion |
Primary outcome
Adverse events assessment
Time frame: From baseline to day 28
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Blood oxygen saturation
Time frame: From baseline to day 14
Evaluation of Pneumonia Improvement
4 secondary outcomes
Intensive care unit-free days
Time frame: Up to day 8
Clinical symptoms
Time frame: From baseline to day 14
Respiratory efficacy
Time frame: From baseline to day 7
Biomarkers concentrations in plasma
Time frame: At baseline, 7, 14, 28 days after the first intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2020.
- Individual participant dataSharing planned: Yes
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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.
Abdol Hossein Shahverdi study chair
Royan Institute
Hossein Baharvand, Professor principal investigator
Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cells Biology & Technology, Iran
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 Cell therapy protocol 1 and Cell therapy protocol 2 in people with Covid-19, run by Royan Institute at 1 site in Iran.
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 8 inclusion and 11 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 30 Apr 2020. 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 Iran. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Masoumeh Nouri (00982127635512, masoume.nouri2002@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events assessment (time frame: From baseline to day 28). 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?
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 30 Apr 2020.