Severe PneumoniaPhase 1NCT04282928
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonian
A Phase 1 study testing Human umbilical cord mesenchymal stem cells and Routine treatment in people with Severe Pneumonia, run by Shanghai East Hospital at 1 site in China.
Trial summary
The purpose of this clinical study is to answer the questions: 1. Is the proposed intervention safe? 2. Is the proposed intervention effective in improving the health of subjects with severe viral pneumonia？ Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Severe Pneumonia
- What is being tested?
- Human umbilical cord mesenchymal stem cells and Routine treatment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Feb 2020to Mar 2021
- 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
- The age is 18-75 years old (inclusive), and the gender is not limited;
- According to the diagnosis standard of viral pneumonia in the influenza diagnosis and treatment plan (2019 version), patients with severe viral pneumonia were diagnosed.
- Diagnostic criteria of viral pneumonia: with clinical manifestations of influenza, with one or more of the following pathogenic test results positive: 1) influenza virus nucleic acid test positive. 2) influenza antigen was positive. 3) the culture of influenza virus was positive. 4) the level of influenza virus specific IgG antibody in the acute and recovery serum was 4 times or more higher. Diagnosis criteria of severe viral pneumonia: the confirmed patients meet any of the following criteria: 1) continuous high fever for more than 3 days, accompanied by severe cough, expectoration, blood sputum, or chest pain; 2) rapid respiratory rate, dyspnea, cyanosis of mouth and lips; 3) mental changes: slow response, drowsiness, agitation, convulsion, etc.; 4) severe vomiting, diarrhea, dehydration; 5) pneumonia; 6 ）7. Other clinical conditions requiring hospitalization
- 20kg / m2 ≤ BMI ≤ 30 kg / m2;
- Volunteer to participate in the clinical study and sign the written informed consent.
Who cannot join
- Long term use of immunosuppressive drugs or organ transplantation;
- T lymphocyte abnormality (the use of allogeneic may be considered, according to the clinical opinion), HIV positive;
- High allergic constitution or severe allergic history, especially IL-2 allergic history;
- Pregnant and lactating women;
- Patients with a history of serious autoimmune diseases; those who are allergic to all biological agents in the treatment, such as IL-2;
- Patients with serious complications: Patients with chronic cardiac insufficiency (NYHA cardiac function grade IV), chronic renal insufficiency (CKD stage 4 or above), chronic liver insufficiency (child Pugh score > 12), and patients with malignant tumors.
- There are other situations that the researcher thinks are not suitable for participating in this clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Singlecenter, Randomized, Open Lable, Intervention Controlled Clinical Study on the Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonia
The purpose of this clinical study is to answer the questions:
- Is the proposed intervention safe?
- Is the proposed intervention effective in improving the health of subjects with severe viral pneumonia？
Read the detailed description
Viral pneumonia is an acute respiratory infectious disease caused by respiratory viruses. It is mainly caused by the invasion of respiratory viruses such as influenza virus and adenovirus into the lower respiratory tract. Every winter and spring is the epidemic season. Influenza virus and adenovirus have high infectivity and pathogenicity. The rapid progress of some patients may be caused by acute respiratory distress syndrome (ARDS) or multiple organ dysfunction And died of complications. The fatality rate of severe patients is 9.8% - 60%. Most of the dead cases were the elderly and the patients with basic diseases. In addition to the complications, the main cause of death is ARDS caused by virus infection, on the other hand, the basic immune function of the elderly is poor, so it is difficult to form an effective antiviral response in response to virus infection. The direct destruction of the alveolar epithelial barrier and the systemic inflammatory response induced by the infection, namely, the destruction of the alveolar capillary barrier by the inflammatory waterfall, are the important pathogenesis of ARDS. How to effectively regulate the inflammatory response, prevent the inflammatory exudation and edema of the lungs, improve oxygenation, and reduce organ damage; at the same time, how to effectively improve the basic immune function and enhance the anti-virus immune response of such patients, has become the key to the success of the treatment of patients with severe viral pneumonia.
Umbilical cord mesenchymal stem cells (UC-MSCs) can differentiate into the different germ layers and play an important role in immune regulation and damage repair regulation. Clinical trials have shown that MSC is safe and effective in the treatment of acute lung injury and pulmonary fibrosis, and it can improve the immune function of patients with viral infectious diseases. Hence, intravenous infusion of HUC-MSCs is attractive therapy against severe viral pneumonia.
This is a randomized, singlecenter, open lable, intervention controlled clinical trial. The participants (n = 40) will be randomly distributed into two groups. The routine treatment group (n = 20) will receive the treatment according to "Influenza diagnosis and treatment plan (2019 version)", the HUC-MSCs adjuvant Group (n = 20) will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment once at day 1 after joining. Follow-up duration is 90 days. The difference of 90 day mortality and average length of stay between the two groups will be observed and recorded. The changes of inflammatory index, viral load, oxygenation index and pulmonary imaging will be monitored at different time points after treatment in the two groups. The serious adverse events (SAEs) and adverse events (AEs) will be observed during the period.
The intent of this study is to explore the efficacy of HUC-MSCs in the treatment of severe viral pneumonia through improving the antiviral immune response of patients, reduce the lung inflammatory damage caused by the virus and the pulmonary interstitial fibrosis after the injury, and finally achieve the goal of reducing the mortality and improving the prognosis of severe patients, and to evaluate the safety.
- Conditions
- Severe Pneumonia
- Being tested
- Human umbilical cord mesenchymal stem cells, Routine treatment
- Keywords
- Umbilical Cord Mesenchymal Stem Cells, Severe viral Pneumonia
- Medical subject headings
- Pneumonia, Pneumonia, Viral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human umbilical cord mesenchymal stem cellsBiological
Definitive Human umbilical cord mesenchymal stem cells selected by immunomodulatory assay through coculture with BV2 cell
Routine treatmentProcedure or surgery
According to"Influenza diagnosis and treatment plan (2019 version)"
| Study group | Role | What they receive |
|---|---|---|
| Routine treatment group | Active comparator | Participants will receive the treatment according to the treatment principle of severe and critical cases in "Influenza diagnosis and treatment plan (2019 version)" Receives: Procedure: Routine treatment |
| HUC-MSCs adjuvant Group | Experimental | Participants will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment. Receives: Biological: Human umbilical cord mesenchymal stem cells; Procedure: Routine treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
The difference of 90 day mortality between the two groups will be observed and recorded
Measured: 90 day
average length of stay
The difference of average length of stay between the two groups will be observed and recorded
Measured: 90 day
Secondary outcomes (6)
Changes of inflammatory index - the number of leukocyte or lymphocyte
Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood of the patients will be collected to detect the number of leukocyte (10^9/L) or lymphocyte (10^9/L).
Measured: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of inflammatory index - the percentage of lymphocytes
Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood of the patients will be collected to detect the percentage of lymphocytes(%).
Measured: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of inflammatory index - cytokines
Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood serum of the patients will be collected to detect the level of CRP, SAA, ESR, PCT and IL-6 (μg/L).
Measured: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of oxygenation index
Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the arterial blood of the patients will be analyzed and the oxygenation index (mmHg) will be calculated according to the oxygen concentration of the patients. The change trend of the oxygenation index will be observed.
Measured: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Throat swab/blood viral load
Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th days after the infusion, the throat swabs and peripheral blood were collected respectively. The RNA copies of the virus will be detected by RT-PCR. The change trend of the viral load in the throat swabs/peripheral blood of the patients in each group will be observed after the treatment with different regimens, and the difference of the viral load between different groups will be compared
Measured: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Chest imaging outcome
Two senior (associate chief physician and above) respiratory radiologists read the films independently. The chest CT images of the two groups will be evaluated before UC-MSCs infusion and on the 7th, 30th and 90th day after UC MSCs infusion. The changes of chest CT images at different time points before and after treatment will be observed and the differences between different treatment groups will be compared.
Measured: Day 0, Day 7, Day 30, Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2020
- Study startFeb 2020 (estimated)
- Primary completionJan 2021 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe PneumoniaStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai East Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhongmin Liu, MD/Ph.D, Principal investigator, Shanghai East Hospital, Tongji University, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04282928
- Sponsor's protocol ID
- EC.D（BG）.013.02.0
- Status last verified
- Feb 2020
- First submitted
- 13 Feb 2020
- Last updated
- 25 Feb 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Singlecenter, Randomized, Open Lable, Intervention Controlled Clinical Study on the Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonia
- ClinicalTrials.gov ID
- NCT04282928
- Acronym / sponsor ID
- EC.D（BG）.013.02.0
- Conditions
- Severe Pneumonia
- Keywords
- Umbilical Cord Mesenchymal Stem Cells, Severe viral Pneumonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Shanghai East HospitalUniversity, hospital or other
- Study start
- Feb 2020 (estimated)
- Primary completion
- Jan 2021 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 25 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.
The purpose of this clinical study is to answer the questions:
- Is the proposed intervention safe?
- Is the proposed intervention effective in improving the health of subjects with severe viral pneumonia？
Detailed description
Viral pneumonia is an acute respiratory infectious disease caused by respiratory viruses. It is mainly caused by the invasion of respiratory viruses such as influenza virus and adenovirus into the lower respiratory tract. Every winter and spring is the epidemic season. Influenza virus and adenovirus have high infectivity and pathogenicity. The rapid progress of some patients may be caused by acute respiratory distress syndrome (ARDS) or multiple organ dysfunction And died of complications. The fatality rate of severe patients is 9.8% - 60%. Most of the dead cases were the elderly and the patients with basic diseases. In addition to the complications, the main cause of death is ARDS caused by virus infection, on the other hand, the basic immune function of the elderly is poor, so it is difficult to form an effective antiviral response in response to virus infection. The direct destruction of the alveolar epithelial barrier and the systemic inflammatory response induced by the infection, namely, the destruction of the alveolar capillary barrier by the inflammatory waterfall, are the important pathogenesis of ARDS. How to effectively regulate the inflammatory response, prevent the inflammatory exudation and edema of the lungs, improve oxygenation, and reduce organ damage; at the same time, how to effectively improve the basic immune function and enhance the anti-virus immune response of such patients, has become the key to the success of the treatment of patients with severe viral pneumonia.
Umbilical cord mesenchymal stem cells (UC-MSCs) can differentiate into the different germ layers and play an important role in immune regulation and damage repair regulation. Clinical trials have shown that MSC is safe and effective in the treatment of acute lung injury and pulmonary fibrosis, and it can improve the immune function of patients with viral infectious diseases. Hence, intravenous infusion of HUC-MSCs is attractive therapy against severe viral pneumonia.
This is a randomized, singlecenter, open lable, intervention controlled clinical trial. The participants (n = 40) will be randomly distributed into two groups. The routine treatment group (n = 20) will receive the treatment according to "Influenza diagnosis and treatment plan (2019 version)", the HUC-MSCs adjuvant Group (n = 20) will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment once at day 1 after joining. Follow-up duration is 90 days. The difference of 90 day mortality and average length of stay between the two groups will be observed and recorded. The changes of inflammatory index, viral load, oxygenation index and pulmonary imaging will be monitored at different time points after treatment in the two groups. The serious adverse events (SAEs) and adverse events (AEs) will be observed during the period.
The intent of this study is to explore the efficacy of HUC-MSCs in the treatment of severe viral pneumonia through improving the antiviral immune response of patients, reduce the lung inflammatory damage caused by the virus and the pulmonary interstitial fibrosis after the injury, and finally achieve the goal of reducing the mortality and improving the prognosis of severe patients, and to evaluate the safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Routine treatment group | Active comparator | Procedure: Routine treatmentParticipants will receive the treatment according to the treatment principle of severe and critical cases in "Influenza diagnosis and treatment plan (2019 version)" |
| HUC-MSCs adjuvant Group | Experimental | Biological: Human umbilical cord mesenchymal stem cells, Procedure: Routine treatmentParticipants will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The age is 18-75 years old (inclusive), and the gender is not limited;
- According to the diagnosis standard of viral pneumonia in the influenza diagnosis and treatment plan (2019 version), patients with severe viral pneumonia were diagnosed.
- Diagnostic criteria of viral pneumonia: with clinical manifestations of influenza, with one or more of the following pathogenic test results positive: 1) influenza virus nucleic acid test positive. 2) influenza antigen was positive. 3) the culture of influenza virus was positive. 4) the level of influenza virus specific IgG antibody in the acute and recovery serum was 4 times or more higher. Diagnosis criteria of severe viral pneumonia: the confirmed patients meet any of the following criteria: 1) continuous high fever for more than 3 days, accompanied by severe cough, expectoration, blood sputum, or chest pain; 2) rapid respiratory rate, dyspnea, cyanosis of mouth and lips; 3) mental changes: slow response, drowsiness, agitation, convulsion, etc.; 4) severe vomiting, diarrhea, dehydration; 5) pneumonia; 6 ）7. Other clinical conditions requiring hospitalization
- 20kg / m2 ≤ BMI ≤ 30 kg / m2;
- Volunteer to participate in the clinical study and sign the written informed consent.
Key exclusion criteria (7 listed)
- Long term use of immunosuppressive drugs or organ transplantation;
- T lymphocyte abnormality (the use of allogeneic may be considered, according to the clinical opinion), HIV positive;
- High allergic constitution or severe allergic history, especially IL-2 allergic history;
- Pregnant and lactating women;
- Patients with a history of serious autoimmune diseases; those who are allergic to all biological agents in the treatment, such as IL-2;
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 |
|---|---|---|
| Human umbilical cord mesenchymal stem cellsDefinitive Human umbilical cord mesenchymal stem cells selected by immunomodulatory assay through coculture with BV2 cell | Biological | HUC-MSCs adjuvant Group |
| Routine treatmentAccording to"Influenza diagnosis and treatment plan (2019 version)" | Procedure or surgery | HUC-MSCs adjuvant Group, Routine treatment group |
Primary outcome
mortality
Time frame: 90 day
The difference of 90 day mortality between the two groups will be observed and recorded
average length of stay
Time frame: 90 day
The difference of average length of stay between the two groups will be observed and recorded
6 secondary outcomes
Changes of inflammatory index - the number of leukocyte or lymphocyte
Time frame: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of inflammatory index - the percentage of lymphocytes
Time frame: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of inflammatory index - cytokines
Time frame: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Changes of oxygenation index
Time frame: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Throat swab/blood viral load
Time frame: Day 0, Day 1，Day 3，Day 7，Day 14，Day 30，Day 60，Day 90
Chest imaging outcome
Time frame: Day 0, Day 7, Day 30, Day 90
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2020.
Related trials for Severe Pneumonia
RecruitingPhase 3
A Clinical Study of Molnupiravir to Prevent Severe Illness From Coronavirus Disease 2019 (COVID-19) in People Who Are High Risk (MK-4482-023)
Coronavirus Disease (COVID-19)
Not yet recruitingPhase 3
Echinocandin Added to Standard Treatment for Severe Pneumocystis Pneumonia
Pneumocystis Jirovecii Pneumonia
RecruitingPhase 3
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Respiratory Tract Diseases, Influenza (Pandemic)
RecruitingPhase 3
A Study of Secutrelvir in Participants With Coronavirus Disease 2019 (COVID-19) Who Are at High Risk for Progression to Severe Disease
SARS-CoV-2
RecruitingPhase 3
Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen
Viral Lung Infection and Acute Respiratory Failure
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.
Zhongmin Liu, MD/Ph.D principal investigator
Shanghai East Hospital, Tongji 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 Human umbilical cord mesenchymal stem cells and Routine treatment in people with Severe Pneumonia, run by Shanghai East 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 5 inclusion and 7 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 25 Feb 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qiang Li, MD/Ph.D ((+86)-13801602220, liqressh@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mortality (time frame: 90 day). 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 25 Feb 2020.