COVID-19Phase 1/2NCT04339660
Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia
A Phase 1/2 study testing UC-MSCs in people with COVID-19, run by Puren Hospital Affiliated to Wuhan University of Science and Technology at 1 site in China.
Trial summary
The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID-19
- What is being tested?
- UC-MSCs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2020to 30 Jun 2020
- Phase
- Phase 1/2
- 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
- Male or female, 18 years old ≤ age ≤ 75years old;
- CT image is characteristic of 2019 novel coronavirus pneumonia;
- Laboratory confirmation of 2019-nCoV infection by reverse transcription polymerase chain reaction (RT-PCR);
- In compliance with the 2019-nCoV pneumonia diagnosis standard (according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and WHO 2019 new coronavirus guidelines standards): (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
- Participant or the authorized agent signed the informed consent form.
- Agree to collect clinical samples.
Who cannot join
- Malignant disease in the past five years;
- Participant with no hope of survival were clinically predicted and only received hospice care, or those who were in a deep coma and did not respond to supportive treatment measures within three hours of admission.
- Participant who are participating in other clinical trials or who have participated in other clinical trials within 3 months.
- Cases of severe shock and respiratory failure.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Puren Hospital Affiliated to Wuhan University of Science and Technology
Wuhan, Hubei, 430081
Yan Liu, MD, +8613387517458, 447822853@qq.com
About this study
The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Read the detailed description
Since December 2019, novel coronavirus disease 2019 (COVID-19) in Wuhan has been fierce and spread rapidly. As of 24:00 on March 4, 2020, China has reported a total of 80567 confirmed cases, 5952 existing critically ill cases, and 3016 dead cases. The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the critically ill cases.
Recently, some clinical researches about the COVID-19 published in The Lancet and The New England Journal of Medicine suggested that massive inflammatory cell infiltration and inflammatory cytokines secretion were found in patients' lungs, alveolar epithelial cells and capillary endothelial cells were damaged, causing acute lung injury. Several reports demonstrated that the first step of the HCoV-19 pathogenesis is that the virus specifically recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike Protein. This receptor is abundant in lung and small intestinal tissues, but is also highly expressed in vascular endothelial cells and smooth muscle cells in almost all organs, including the nervous system and skeletal muscle. The main organ injured by the HCoV-19 is the lung. In fact, HCoV-19 can also involve the nervous system, digestive system, urinary system, blood system and other systems. Therefore, when the initial symptom is discomfort of other systems in the early stage, it is often easy to be misdiagnosed and delay treatment. Moreover, the HCoV-19 is a noncellular form consisting of RNA and protein, which cannot be copied independently. It needs to bind to cell surface receptors to enter the cell to complete the replication, and then be released again. Therefore, once the HCoV-19 enters the blood circulation, it can easily spread to all systems throughout the body, which may be the pathological mechanism that the HCoV-19 directly or indirectly causes neurological symptoms.
It seems that the key to cure the COVID-19 pneumonia is to inhibit the inflammatory response, resulting to reduce the damage of alveolar epithelial cells and endothelial cells and repair the function of the lung. MSCs, owing to their powerful immunomodulatory ability, may have beneficial effects on preventing or attenuating the cytokine storm.
Mesenchymal stem cells (MSCs) are widely used in basic research and clinical application. They are proved to migrate to damaged tissues, exert antiinflammatory and immunoregulatory functions, promote the regeneration of damaged tissues and inhibit tissue fibrosis. MSCs play a positive role mainly in two ways, namely immunomodulatory effects and differentiation abilities. MSCs can secrete many types of cytokines by paracrine secretion or make direct interactions with immune cells, leading to immunomodulation. Studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses by reducing the levels of proinflammatory cytokines and the recruitment of inflammatory cells into the lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (UC-MSCs) have been widely applied to various diseases due to their convenient collection, no ethical controversy, low immunogenicity, and rapid proliferation rate.
Here we conducted an MSC transplantation pilot study to explore their therapeutic potential for COVID-19 pneumonia patients. To explore the effective treatment of COVID-19 pneumonia for the current prevention and control of novel coronavirus pneumonia to find a key and effective clinical treatment means, to fight against the epidemic.
- Conditions
- COVID-19
- Being tested
- UC-MSCs, Placebo
- Keywords
- COVID-19, UC-MSCs, critically ill, cell transplantation
- Medical subject headings
- COVID-19, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UC-MSCsBiological
1*10E6 UC-MSCs /kg body weight suspended in 100mL saline
PlaceboOther
100mL saline intravenously
| Study group | Role | What they receive |
|---|---|---|
| UC-MSCs treatment group | Experimental | Participants will receive conventional and treatment with MSCs, MSCs were suspended in 100 mL of normal saline, and the total number of transplanted cells was calculated by 1*10E6 cells per kilogram of weight. This product is generally a course of treatment, a total of 1 time, depending on the condition of the need to be given again at an interval of 1 week. Receives: Biological: UC-MSCs |
| Control group | Placebo comparator | Participants will receive conventional treatment and Placebo intravenously. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP)
Improvement and recovery time of inflammatory and immune factors
Measured: Observe the immune function of the participants within 4 weeks
Blood oxygen saturation
Evaluation of Pneumonia change
Measured: Monitor blood oxygen saturation of the participants within 4 weeks
Secondary outcomes (6)
Rate of mortality within 28-days
Marker for efficacy of treatment
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Size of lesion area by chest imaging
Evaluation of Pneumonia change
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
CD4+ and CD8+ T cells count
Marker of Immunology and inflammation
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Peripheral blood count recovery time
Degree of infection
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.)
Indirect response to lung function
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
COVID-19 nucleic acid negative time
Clearance time of COVID-19 in participant
Measured: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start1 Feb 2020
- Primary completion30 Jun 2020 (estimated)
- Study completion30 Jun 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Puren Hospital Affiliated to Wuhan University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai University, Qingdao Co-orient Watson Biotechnology group co. LTD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04339660
- Sponsor's protocol ID
- Pr20200402
- Status last verified
- Apr 2020
- First submitted
- 2 Apr 2020
- Last updated
- 9 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia
- ClinicalTrials.gov ID
- NCT04339660
- Acronym / sponsor ID
- Pr20200402
- Conditions
- COVID-19
- Keywords
- COVID-19, UC-MSCs, critically ill, cell transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Puren Hospital Affiliated to Wuhan University of Science and TechnologyUniversity, hospital or other
- Collaborators
- Shanghai University, Qingdao Co-orient Watson Biotechnology group co. LTD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 9 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.
The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Detailed description
Since December 2019, novel coronavirus disease 2019 (COVID-19) in Wuhan has been fierce and spread rapidly. As of 24:00 on March 4, 2020, China has reported a total of 80567 confirmed cases, 5952 existing critically ill cases, and 3016 dead cases. The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the critically ill cases.
Recently, some clinical researches about the COVID-19 published in The Lancet and The New England Journal of Medicine suggested that massive inflammatory cell infiltration and inflammatory cytokines secretion were found in patients' lungs, alveolar epithelial cells and capillary endothelial cells were damaged, causing acute lung injury. Several reports demonstrated that the first step of the HCoV-19 pathogenesis is that the virus specifically recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike Protein. This receptor is abundant in lung and small intestinal tissues, but is also highly expressed in vascular endothelial cells and smooth muscle cells in almost all organs, including the nervous system and skeletal muscle. The main organ injured by the HCoV-19 is the lung. In fact, HCoV-19 can also involve the nervous system, digestive system, urinary system, blood system and other systems. Therefore, when the initial symptom is discomfort of other systems in the early stage, it is often easy to be misdiagnosed and delay treatment. Moreover, the HCoV-19 is a noncellular form consisting of RNA and protein, which cannot be copied independently. It needs to bind to cell surface receptors to enter the cell to complete the replication, and then be released again. Therefore, once the HCoV-19 enters the blood circulation, it can easily spread to all systems throughout the body, which may be the pathological mechanism that the HCoV-19 directly or indirectly causes neurological symptoms.
It seems that the key to cure the COVID-19 pneumonia is to inhibit the inflammatory response, resulting to reduce the damage of alveolar epithelial cells and endothelial cells and repair the function of the lung. MSCs, owing to their powerful immunomodulatory ability, may have beneficial effects on preventing or attenuating the cytokine storm.
Mesenchymal stem cells (MSCs) are widely used in basic research and clinical application. They are proved to migrate to damaged tissues, exert antiinflammatory and immunoregulatory functions, promote the regeneration of damaged tissues and inhibit tissue fibrosis. MSCs play a positive role mainly in two ways, namely immunomodulatory effects and differentiation abilities. MSCs can secrete many types of cytokines by paracrine secretion or make direct interactions with immune cells, leading to immunomodulation. Studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses by reducing the levels of proinflammatory cytokines and the recruitment of inflammatory cells into the lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (UC-MSCs) have been widely applied to various diseases due to their convenient collection, no ethical controversy, low immunogenicity, and rapid proliferation rate.
Here we conducted an MSC transplantation pilot study to explore their therapeutic potential for COVID-19 pneumonia patients. To explore the effective treatment of COVID-19 pneumonia for the current prevention and control of novel coronavirus pneumonia to find a key and effective clinical treatment means, to fight against the epidemic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| UC-MSCs treatment group | Experimental | Biological: UC-MSCsParticipants will receive conventional and treatment with MSCs, MSCs were suspended in 100 mL of normal saline, and the total number of transplanted cells was calculated by 1*10E6 cells per kilogram of weight. This product is generally a course of treatment, a total of 1 time, depending on the condition of the need to be given again at an interval of 1 week. |
| Control group | Placebo comparator | Other: PlaceboParticipants will receive conventional treatment and Placebo intravenously. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, 18 years old ≤ age ≤ 75years old;
- CT image is characteristic of 2019 novel coronavirus pneumonia;
- Laboratory confirmation of 2019-nCoV infection by reverse transcription polymerase chain reaction (RT-PCR);
- In compliance with the 2019-nCoV pneumonia diagnosis standard (according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and WHO 2019 new coronavirus guidelines standards): (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
- Participant or the authorized agent signed the informed consent form.
Key exclusion criteria (4 listed)
- Malignant disease in the past five years;
- Participant with no hope of survival were clinically predicted and only received hospice care, or those who were in a deep coma and did not respond to supportive treatment measures within three hours of admission.
- Participant who are participating in other clinical trials or who have participated in other clinical trials within 3 months.
- Cases of severe shock and respiratory failure.
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 |
|---|---|---|
| UC-MSCs1*10E6 UC-MSCs /kg body weight suspended in 100mL saline | Biological | UC-MSCs treatment group |
| Placebo100mL saline intravenously | Other | Control group |
Primary outcome
The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP)
Time frame: Observe the immune function of the participants within 4 weeks
Improvement and recovery time of inflammatory and immune factors
Blood oxygen saturation
Time frame: Monitor blood oxygen saturation of the participants within 4 weeks
Evaluation of Pneumonia change
6 secondary outcomes
Rate of mortality within 28-days
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Size of lesion area by chest imaging
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
CD4+ and CD8+ T cells count
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Peripheral blood count recovery time
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.)
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
COVID-19 nucleic acid negative time
Time frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2020.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing UC-MSCs in people with COVID-19, run by Puren Hospital Affiliated to Wuhan University of Science and Technology 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 6 inclusion and 4 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 9 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 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. Some participants in this study may receive a placebo. 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 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Yan Liu, MD (+8613387517458, 447822853@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP) (time frame: Observe the immune function of the participants within 4 weeks). 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 9 Apr 2020.