Clinical trial NCT04313647: A Tolerance Clinical Study on Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers
Official title: A Tolerance Clinical Study On Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: mesenchymal stem cells
exosomes
mesh nebulizer
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2020-03-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: MSCs-exosomes
Primary purpose: TREATMENT

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.)

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE)
timeFrame: from Day 0 to Day 7
Secondary outcomes:
Other outcomes:
measure: Alanine Aminotransferase (ALT) (IU/L)
timeFrame: day 0 and day 7
measure: Creatinine (Cr) (μmol/L)
timeFrame: day 0 and day 7
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Jieming Qu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shi MM, Yang QY, Monsel A, Yan JY, Dai CX, Zhao JY, Shi GC, Zhou M, Zhu XM, Li SK, Li P, Wang J, Li M, Lei JG, Xu D, Zhu YG, Qu JM. Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. J Extracell Vesicles. 2021 Aug;10(10):e12134. doi: 10.1002/jev2.12134. Epub 2021 Aug 14.