Back to resultsA Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
Primary Purpose
Coronavirus
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
MSCs-derived exosomes
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus focused on measuring mesenchymal stem cells, exosome, nebulization, SARS-CoV-2, novel coronavirus pneumonia
Eligibility Criteria
Inclusion Criteria:
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:
- Respiratory failure, and requirement for mechanical ventilation
- Shock
- Other organ failure and requirement for ICU monitoring
Exclusion Criteria:
- 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;
- 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.
Sites / Locations
- Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MSCs-derived Exosomes Treatment Group
Arm Description
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).
Outcomes
Primary Outcome Measures
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)
Time to clinical improvement (TTIC)
Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Secondary Outcome Measures
Number of patients weaning from mechanical ventilation
Number of patients weaning from mechanical ventilation within 28 days
Duration (days) of ICU monitoring
Duration (days) of ICU monitoring within 28 days
Duration (days) of vasoactive agents usage
Duration (days) of vasoactive agents using within 28 days
Duration (days) of mechanical ventilation supply
Duration (days) of mechanical ventilation supply among survivors
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
Rate of mortality
Rate of mortality within 28 days
Full Information
NCT ID
NCT04276987
First Posted
February 16, 2020
Last Updated
September 3, 2020
Sponsor
Ruijin Hospital
Collaborators
Shanghai Public Health Clinical Center, Wuhan Jinyintan Hospital, Wuhan, China, Cellular Biomedicine Group Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04276987
Brief Title
A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
February 15, 2020 (Actual)
Primary Completion Date
May 31, 2020 (Actual)
Study Completion Date
July 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ruijin Hospital
Collaborators
Shanghai Public Health Clinical Center, Wuhan Jinyintan Hospital, Wuhan, China, Cellular Biomedicine Group Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus
Keywords
mesenchymal stem cells, exosome, nebulization, SARS-CoV-2, novel coronavirus pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MSCs-derived Exosomes Treatment Group
Arm Type
Experimental
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
MSCs-derived exosomes
Intervention Description
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).
Primary Outcome Measure Information:
Title
Adverse reaction (AE) and severe adverse reaction (SAE)
Description
Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Time Frame
Up to 28 days
Title
Time to clinical improvement (TTIC)
Description
Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Number of patients weaning from mechanical ventilation
Description
Number of patients weaning from mechanical ventilation within 28 days
Time Frame
Up to 28 days
Title
Duration (days) of ICU monitoring
Description
Duration (days) of ICU monitoring within 28 days
Time Frame
Up to 28 days
Title
Duration (days) of vasoactive agents usage
Description
Duration (days) of vasoactive agents using within 28 days
Time Frame
Up to 28 days
Title
Duration (days) of mechanical ventilation supply
Description
Duration (days) of mechanical ventilation supply among survivors
Time Frame
Up to 28 days
Title
Number of patients with improved organ failure
Description
Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs
Time Frame
Up to 28 days
Title
Rate of mortality
Description
Rate of mortality within 28 days
Time Frame
Up to 28 days
Other Pre-specified Outcome Measures:
Title
Sequential organ failure assessment (SOFA) score
Description
Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)
Time Frame
Every day for 28 days
Title
Lymphocyte Count (10E9/L)
Description
Records of Blood routine test
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
C-reactive protein (CRP) (mg/L)
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
Lactate dehydrogenase (U/L)
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
D-dimer (mg/L)
Description
Coagulation function
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
pro-type B natriuretic peptide (pro-BNP) (pg/ml)
Description
Records of heart failure
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
IL-1β (pg/ml)
Description
Record of serum cytokine
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
IL-2R (ng/L)
Description
Record of serum cytokine
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
IL-6 (ng/L)
Description
Record of serum cytokine
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
IL-8 (ng/L)
Description
Record of serum cytokine
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
Chest imaging
Description
Computed tomography or X-ray
Time Frame
Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available
Title
Time to SARS-CoV-2 RT-PCR negativity
Description
Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens
Time Frame
Up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
Respiratory failure, and requirement for mechanical ventilation
Shock
Other organ failure and requirement for ICU monitoring
Exclusion Criteria:
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;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie-ming Qu, MD.,PhD.
Organizational Affiliation
Ruijin Hospital, Medical School of Shanghai Jiaotong University Shanghai, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
all IPD that underlie results in a publication
IPD Sharing Time Frame
Starting 6 months after publication
Citations:
PubMed Identifier
35619189
Citation
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.
Results Reference
derived
Learn more about this trial
A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
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