Healthy
Conditions
Keywords
mesenchymal stem cells, exosomes, mesh nebulizer
Brief summary
Exosomes are naturally occurring nanosized vesicles and comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. These vesicles have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Exosomes are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body, and can influence tissue responses to injury, infection, and disease. 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 were improved. It is highly likely that MSCs-Exo have the similar therapeutic effect on inoculation pneumonia as MSCs themselves. This clinical study will be performed to evaluate the safety and tolerance of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in healthy volunteers.
Detailed description
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 were improved. It is highly likely that MSCs-Exo have the similar 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 study, therefore, is to explore the safety and efficiency as well as provide a clinical dose reference for the subsequent trails of aerosol inhalation of MSCs-Exo in the treatment of severe lung diseases (including severe lung infection, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), etc.)
Interventions
BIOLOGICAL1X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (2.0\*10\^8 nano vesicles/3 ml)
BIOLOGICAL2X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (4.0\*10\^8 nano vesicles/3 ml)
BIOLOGICAL4X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (8.0\*10\^8 nano vesicles/3 ml)
BIOLOGICAL6X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (12.0\*10\^8 nano vesicles/3 ml)
BIOLOGICAL8X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (16.0\*10\^8 nano vesicles/3 ml)
Sponsors
Shanghai AbelZeta Ltd.
Ruijin Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
MSCs-exosomes
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy volunteers. 2. Age: 19-45, males and females. 3. The weight is within ± 10% of the standard weight \[standard weight (kg) = 0.7 × (height cm-80)\]. 4. Examination indices of heart, liver, kidney and blood are all within the normal range. 5. According to Good Clinical Practice (GCP), volunteers who understand and voluntarily sign the consent form before this study.
Exclusion criteria
1. Women in pregnancy or lactation. 2. Primary diseases of important organs. 3. Mentally or physically disabled patients. 4. Suspected or definite history of alcohol and drug abuse. 5. According to the investigator's judgment, there is a low possibility of enrollment (such as frailty, etc.). 6. Volunteers who are allergic to the components of this medicine, or have a history of allergies to two or more drugs or food. 7. Volunteers who have diseases (such as insomnia) and are using other preventive and therapeutic drugs before this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | from Day 0 to Day 7 | Safety evaluation within 7 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Alanine Aminotransferase (ALT) (IU/L) | day 0 and day 7 | one of the indexes about liver function |
| Creatinine (Cr) (μmol/L) | day 0 and day 7 | One of the indexes about kidney function |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1X Level Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (2.0\*10E8 nano vesicles/3 ml)
1X level of MSCs-Exo: Once aerosol inhalation of MSCs-derived exosomes (2.0\*10E8 nano vesicles/3 ml) | 3 |
| 2X Level Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (4.0\*10E8 nano vesicles/3 ml)
2X level of MSCs-Exo: Once aerosol inhalation of MSCs-derived exosomes (4.0\*10E8 nano vesicles/3 ml) | 3 |
| 4X Level Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (8.0\*10E8 nano vesicles/3 ml)
4X level of MSCs-Exo: Once aerosol inhalation of MSCs-derived exosomes (8.0\*10E8 nano vesicles/3 ml) | 6 |
| 6X Level Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (12.0\*10E8 nano vesicles/3 ml)
6X level of MSCs-Exo: Once aerosol inhalation of MSCs-derived exosomes (12.0\*10E8 nano vesicles/3 ml) | 6 |
| 8X Level Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (16.0\*10E8 nano vesicles/3 ml)
8X level of MSCs-Exo: Once aerosol inhalation of MSCs-derived exosomes (16.0\*10E8 nano vesicles/3 ml) | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | 1X Level | 2X Level | 4X Level | 6X Level | 8X Level | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 26 years | 26 years | 25 years | 25 years | 25.5 years | 25 years |
| Comorbidity | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Chinese | 3 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Region of Enrollment China | 3 participants | 3 participants | 6 participants | 6 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 13 Participants |
| Smoking history | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE)
Safety evaluation within 7 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Time frame: from Day 0 to Day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1X Level | Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | 1 Participants |
| 2X Level | Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | 0 Participants |
| 4X Level | Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | 0 Participants |
| 6X Level | Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | 0 Participants |
| 8X Level | Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | 1 Participants |
Other Pre-specified
Alanine Aminotransferase (ALT) (IU/L)
one of the indexes about liver function
Time frame: day 0 and day 7
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 0 | 16 IU/L |
| 1X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 7 | 20 IU/L |
| 2X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 0 | 21 IU/L |
| 2X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 7 | 24 IU/L |
| 4X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 0 | 24 IU/L |
| 4X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 7 | 23.5 IU/L |
| 6X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 7 | 16 IU/L |
| 6X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 0 | 17.5 IU/L |
| 8X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 0 | 15.5 IU/L |
| 8X Level | Alanine Aminotransferase (ALT) (IU/L) | Day 7 | 15.5 IU/L |
Other Pre-specified
Creatinine (Cr) (μmol/L)
One of the indexes about kidney function
Time frame: day 0 and day 7
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1X Level | Creatinine (Cr) (μmol/L) | Day 0 | 67 μmol/L |
| 1X Level | Creatinine (Cr) (μmol/L) | Day 7 | 64 μmol/L |
| 2X Level | Creatinine (Cr) (μmol/L) | Day 0 | 83 μmol/L |
| 2X Level | Creatinine (Cr) (μmol/L) | Day 7 | 77 μmol/L |
| 4X Level | Creatinine (Cr) (μmol/L) | Day 7 | 86 μmol/L |
| 4X Level | Creatinine (Cr) (μmol/L) | Day 0 | 82.5 μmol/L |
| 6X Level | Creatinine (Cr) (μmol/L) | Day 0 | 74.5 μmol/L |
| 6X Level | Creatinine (Cr) (μmol/L) | Day 7 | 74.5 μmol/L |
| 8X Level | Creatinine (Cr) (μmol/L) | Day 0 | 81 μmol/L |
| 8X Level | Creatinine (Cr) (μmol/L) | Day 7 | 80 μmol/L |