CoronavirusPhase 1NCT04276987
A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
A Phase 1 study testing MSCs-derived exosomes in people with Coronavirus, run by Ruijin Hospital at 1 site in China.
Trial summary
In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronavirus
- What is being tested?
- MSCs-derived exosomes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 15 Feb 2020to 31 Jul 2020
- Phase
- Phase 1
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Willingness of study participant to accept this treatment arm, and signed informed consent; 2.Male or female, aged at 18 years (including) to 75 years old; 3.Patients with confirmed novel coronavirus pneumonia; 4.Confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from respiratory tract or blood specimens; 5.Diagnostic criteria of "Severe" or " Critical":
- Severe, comply with any of the following:
- Respiratory distress, Respiratory rate (RR) ≥ 30 times/min
- Pulse oxygen saturation (SpO2) at rest ≤ 93%
- Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300mmHg
- Critical, comply with any of the following:
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- Respiratory failure, and requirement for mechanical ventilation
- Shock
- Other organ failure and requirement for ICU monitoring
Who cannot join
- Allergic or hypersensitive to any of the ingredients;
- Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses;
- Obstructive HABP/VABP induced by lung cancer or other known causes;
- Carcinoid syndrome;
- History of long-term use of immunosuppressive agents;
- History of epilepsy and requirement for continuous anticonvulsant treatment or anticonvulsant treatment received within the last 3 years;
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- History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
- Undergoing hemodialysis or peritoneal dialysis;
- Estimated or actual rate of creatinine clearance < 15 ml/min;
- History of moderate and severe liver disease (Child-Pugh score >12);
- Expectation of receiving any of following medications during the study:
- Receiving continuous valproic acid or sodium valproate within the first 2 weeks prior to screening
- Receiving 5-transtryptamine reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists or monoamine oxidase inhibitors within the first 2 weeks prior to screening
- Incapable of understanding study protocol;
- History of deep venous thrombosis or pulmonary embolism within the last 3 years;
- Undergoing ECMO or high-frequency oscillatory ventilation support;
- HIV, hepatitis virus, or syphilis infection;
- Period of pregnancy or lactation, or planned pregnancy within 6 months;
- Any condition of unsuitable for the study determined by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
About this study
Official title: A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia
In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).
Read the detailed description
Since December 2019, SARS-CoV-2 infection has become a worldwide urgent public health event, especially in China. As of February 13, 2020, over 63,000 cases have been confirmed with over 10,200 severe cases in mainland of China. There is currently no vaccine or specific antiviral treatment existing for SARS-CoV-2 infection. Although symptomatic and supportive care are recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes, with mortality of ~10%. Therefore, it is urgent to find a safe and effective therapeutic approach to patients with severe coronavirus disease-19(COVID-19) characterized by an severe acute respiratory impairment.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and outcome are improved. It is highly likely that MSCs-Exo have the same therapeutic effect on inoculation pneumonia as MSCs themselves.
Although human bone marrow MSCs have been safely administered in patients with ARDS and septic shock (phase I/II trials), it seems safer to deliver MSCs-Exo rather than live MSCs. The intravenous administration of MSCs may result in aggregating or clumping in the injured microcirculation and carries the risk of mutagenicity and oncogenicity, which do not exist by treating with nebulized MSCs-Exo. Another advantage of MSCs-Exo over MSCs is the possibility of storing them for several weeks/months allowing their safe transportation and delayed therapeutic use.
The purpose of this single-arm design, open label, combined interventional clinical trial, therefore, is to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
- Conditions
- Coronavirus
- Being tested
- MSCs-derived exosomes
- Keywords
- mesenchymal stem cells, exosome, nebulization, SARS-CoV-2, novel coronavirus pneumonia
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSCs-derived exosomesBiological
5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5).
| Study group | Role | What they receive |
|---|---|---|
| MSCs-derived Exosomes Treatment Group | Experimental | Conventional treatment and aerosol inhalation of MSCs-derived exosomes treatment participants will receive conventional treatment and 5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5). Receives: Biological: MSCs-derived exosomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse reaction (AE) and severe adverse reaction (SAE)
Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Measured: Up to 28 days
Time to clinical improvement (TTIC)
Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Measured: Up to 28 days
Secondary outcomes (6)
Number of patients weaning from mechanical ventilation
Number of patients weaning from mechanical ventilation within 28 days
Measured: Up to 28 days
Duration (days) of ICU monitoring
Duration (days) of ICU monitoring within 28 days
Measured: Up to 28 days
Duration (days) of vasoactive agents usage
Duration (days) of vasoactive agents using within 28 days
Measured: Up to 28 days
Duration (days) of mechanical ventilation supply
Duration (days) of mechanical ventilation supply among survivors
Measured: Up to 28 days
Number of patients with improved organ failure
Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs
Measured: Up to 28 days
Rate of mortality
Rate of mortality within 28 days
Measured: Up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start15 Feb 2020
- Primary completion31 May 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CoronavirusStudies of the same condition, open and under way.
- More trials run by Ruijin 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Public Health Clinical Center, Wuhan Jinyintan Hospital, Wuhan, China, Shanghai AbelZeta Ltd.
- Responsible party
- Sponsor
- Investigators
- Jie-ming Qu, MD.,PhD., Principal investigator, Ruijin Hospital, Medical School of Shanghai Jiaotong University Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276987
- Sponsor's protocol ID
- MEXCOVID
- Status last verified
- Sep 2020
- First submitted
- 16 Feb 2020
- Last updated
- 7 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Publications
Zhu YG, Shi MM, Monsel A, Dai CX, Dong X, Shen H, Li SK, Chang J, Xu CL, Li P, Wang J, Shen MP, Ren CJ, Chen DC, Qu JM. Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem Cell Res Ther. 2022 May 26;13(1):220. doi: 10.1186/s13287-022-02900-5.
PubMed 35619189
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia
- ClinicalTrials.gov ID
- NCT04276987
- Acronym / sponsor ID
- MEXCOVID
- Conditions
- Coronavirus
- Keywords
- mesenchymal stem cells, exosome, nebulization, SARS-CoV-2, novel coronavirus pneumonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Collaborators
- Shanghai Public Health Clinical Center, Wuhan Jinyintan Hospital, Wuhan, China, Shanghai AbelZeta Ltd.
- Study start
- 15 Feb 2020 (actual)
- Primary completion
- 31 May 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 19 Feb 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.
In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).
Detailed description
Since December 2019, SARS-CoV-2 infection has become a worldwide urgent public health event, especially in China. As of February 13, 2020, over 63,000 cases have been confirmed with over 10,200 severe cases in mainland of China. There is currently no vaccine or specific antiviral treatment existing for SARS-CoV-2 infection. Although symptomatic and supportive care are recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes, with mortality of ~10%. Therefore, it is urgent to find a safe and effective therapeutic approach to patients with severe coronavirus disease-19(COVID-19) characterized by an severe acute respiratory impairment.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and outcome are improved. It is highly likely that MSCs-Exo have the same therapeutic effect on inoculation pneumonia as MSCs themselves.
Although human bone marrow MSCs have been safely administered in patients with ARDS and septic shock (phase I/II trials), it seems safer to deliver MSCs-Exo rather than live MSCs. The intravenous administration of MSCs may result in aggregating or clumping in the injured microcirculation and carries the risk of mutagenicity and oncogenicity, which do not exist by treating with nebulized MSCs-Exo. Another advantage of MSCs-Exo over MSCs is the possibility of storing them for several weeks/months allowing their safe transportation and delayed therapeutic use.
The purpose of this single-arm design, open label, combined interventional clinical trial, therefore, is to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MSCs-derived Exosomes Treatment Group | Experimental | Biological: MSCs-derived exosomesConventional treatment and aerosol inhalation of MSCs-derived exosomes treatment participants will receive conventional treatment and 5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1.Willingness of study participant to accept this treatment arm, and signed informed consent; 2.Male or female, aged at 18 years (including) to 75 years old; 3.Patients with confirmed novel coronavirus pneumonia; 4.Confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from respiratory tract or blood specimens; 5.Diagnostic criteria of "Severe" or " Critical":
- Severe, comply with any of the following:
- Critical, comply with any of the following:
Key exclusion criteria (19 listed)
- Allergic or hypersensitive to any of the ingredients;
- Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses;
- Obstructive HABP/VABP induced by lung cancer or other known causes;
- Carcinoid syndrome;
- History of long-term use of immunosuppressive agents;
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 |
|---|---|---|
| MSCs-derived exosomes5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5). | Biological | MSCs-derived Exosomes Treatment Group |
Primary outcome
Adverse reaction (AE) and severe adverse reaction (SAE)
Time frame: Up to 28 days
Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Time to clinical improvement (TTIC)
Time frame: Up to 28 days
Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
6 secondary outcomes
Number of patients weaning from mechanical ventilation
Time frame: Up to 28 days
Duration (days) of ICU monitoring
Time frame: Up to 28 days
Duration (days) of vasoactive agents usage
Time frame: Up to 28 days
Duration (days) of mechanical ventilation supply
Time frame: Up to 28 days
Number of patients with improved organ failure
Time frame: Up to 28 days
Rate of mortality
Time frame: Up to 28 days
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 7 Sep 2020.
- Derived from this study: PubMed 35619189Zhu YG, Shi MM, Monsel A, Dai CX, Dong X, Shen H, Li SK, Chang J, Xu CL, Li P, Wang J, Shen MP, Ren CJ, Chen DC, Qu JM. Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem Cell Res Ther. 2022 May 26;13(1):220. doi: 10.1186/s13287-022-02900-5.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
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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.
Jie-ming Qu, MD.,PhD. principal investigator
Ruijin Hospital, Medical School of Shanghai Jiaotong University Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MSCs-derived exosomes in people with Coronavirus, run by Ruijin Hospital at 1 site in China.
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 9 inclusion and 19 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 7 Sep 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 China. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Adverse reaction (AE) and severe adverse reaction (SAE) (time frame: Up to 28 days). 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 NCT04276987, which also lists 1 linked publication.
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 7 Sep 2020.