A Tolerance Clinical Study on Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers

Healthy Clinical Trial

Official title:

A Tolerance Clinical Study On Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04313647
• Other study ID #: MEXVT
• Status: Completed
• Phase: Phase 1
• Start date: March 12, 2020
• Est. completion date: July 31, 2020

Study information

• Verified date: May 2021
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 31, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Respiratory Aspiration

Intervention

Biological:
• 1X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (2.0*10^8 nano vesicles/3 ml)
• 2X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (4.0*10^8 nano vesicles/3 ml)
• 4X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (8.0*10^8 nano vesicles/3 ml)
• 6X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (12.0*10^8 nano vesicles/3 ml)
• 8X level of MSCs-Exo
Once aerosol inhalation of MSCs-derived exosomes (16.0*10^8 nano vesicles/3 ml)

Locations

Country	Name	City	State
China	Ruijin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Ruijin Hospital	Cellular Biomedicine Group Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Alanine Aminotransferase (ALT) (IU/L)	one of the indexes about liver function	day 0 and day 7
Other	Creatinine (Cr) (µmol/L)	One of the indexes about kidney function	day 0 and day 7
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)	from Day 0 to Day 7