Administration of Allogenic UC-MSCs as Adjuvant Therapy for Critically-Ill COVID-19 Patients
Application of Umbilical Cord Mesenchymal Stem Cells as Adjuvant Therapy for Critically-Ill COVID-19 Patients
1 other identifier
interventional
40
1 country
4
Brief Summary
Novel Coronavirus (2019nCoV) or Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) that causes Coronavirus Disease 2019, or known as Covid-19 has recently become a global health emergency since it was first detected in Wuhan, the People Republic of China in December 2019. Since then, the prevalence has rapidly increased worldwide. In Indonesia, by the end of April 2020, around 10,000 patients have been tested positive for Covid-19 infection, with a case fatality rate of around 8%. The pathogenesis of Covid-19 is still under investigation and to our understanding, ACE2 receptors in the alveoli serve as the binding site of the S-protein of envelope spike virus of SARS-CoV-2. TMPRSS2 enzyme aids the fusion between cell membrane and capsid of the virus, allowing penetration of virus into the cell. Vesicles containing virion fuse with cell membrane and released as new virions. Cytopathic effect of the virus and its ability to overcome immune response determines the degree of infection. Differences in immunological profile among degrees of severity of Covid-19 may vary especially for the number of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-6, IL-8, leukemia-inhibiting factors (LIF), immunological markers such as CXCR3+CD4+, CXCR3+CD8+ T cell and CXCR3+ NK cells, implying the ongoing cytokine storm. The previous studies also found increasing number for infection markers such as procalcitonin, ferritin, and C-reactive protein. The decreasing number of anti-inflammatory cytokines in such as IL-10 also supports this finding. Previous studies have shown immunomodulating and anti-inflammatory capacity of the mesenchymal stem cells (MSCs). MSCs contributed to the shifting of pro-inflammatory Th2 into anti-inflammatory Th2. One of the most recent study on the usage of MSCs on Covid-19 patients showed increased expression of leukemia inhibitory factor (LIF), which give rise to inhibitory effect of T lymphocyte and natural killer (NK) cell population. Vascular epithelial growth factor (VEGF) is found increasing following MSCs administration, which indicates the ability to improve the disrupted capillaries due to SARS-Cov-2 infection. The ability of MSCs in differentiating to alveolar cells is proven by the presence of SPM and SPC2, surfactant proteins produced by type II alveolar cells. MSCs are unable to be infected by SARS-CoV-2 since they don't have ACE2 receptors and TMPRSS2 enzyme.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2020
Shorter than P25 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 27, 2020
CompletedStudy Start
First participant enrolled
July 1, 2020
CompletedFirst Posted
Study publicly available on registry
July 7, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2020
CompletedJuly 7, 2020
July 1, 2020
1 month
May 27, 2020
July 2, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Clinical improvement: Presence of dyspnea
Assessing whether the patients still have dyspnea, one of cardinal symptoms of Covid-19, assessed from the respiratory rate
15 days
Clinical improvement: presence of sputum
Assessing whether the patients still have productive cough, one of cardinal symptoms of Covid-19, assessed from lung auscultation
15 days
Clinical improvement: fever
Assessing the presence of fever from measurement of body temperature checking, assessed on daily basis
15 days
Clinical improvement: ventilation status
Assessing whether the patients still require ventilation, one of cardinal symptoms of ARDS in Covid-19, assessed from patients' ability during ventilation weaning phase
15 days
Clinical improvement: blood pressure
Assessing the patients' blood pressure on daily basis
15 days
Clinical improvement: heart rate
Assessing the patients' heart rate on daily basis
15 days
Clinical improvement: respiratory rate
Assessing the patients' respiratory rate on daily basis
15 days
Clinical improvement: oxygen saturation
Assessing the patients' oxygen saturation on daily basis
15 days
Secondary Outcomes (32)
General laboratory outcome from leukocyte level
15 days
General laboratory outcome from lymphocytes level
15 days
General laboratory outcome from blood pH
15 days
General laboratory outcome from blood level of CO2
15 days
General laboratory outcome from blood base excess level
15 days
- +27 more secondary outcomes
Study Arms (2)
Control Group
PLACEBO COMPARATORPatients receive standardized treatment, consisting of Oseltamivir and Azithromycin
Experiment Group
EXPERIMENTALPatients receive intravenous infusion of 1x10\^6 unit of umbilical-cord derived mesenchymal stem cells (UC-MSCs)/kgBW in 100 cc of 0.9% NaCl for 1 hour, in addition to standardized treatment
Interventions
Adjuvant therapy on top of current standardized treatment (Oseltamivir + Azithromycin)
Eligibility Criteria
You may qualify if:
- Patients aged 18-95 years old
- Confirmed for diagnosis of Covid-19 through RT-PCR from nasopharyngeal swab and/or bronchoalveolar lavage for patients under intubation
- Laboratory results showed leukopenia and lymphopenic
- Chest radiography shows pneumonia appearance and/or ground-glass opacity on chest CT-Scan
- Patients/their families are willing to sign the informed consent
You may not qualify if:
- History of malignancy
- Pregnant, or show positive result on pregnancy test
- Patients was/are currently participating in other clinical trials within the last 3 months
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Persahabatan General Hospital
Jakarta, DKI Jakarta, Indonesia
Sulianti Saroso Center for Infectious Disease
Jakarta, DKI Jakarta, Indonesia
Cipto Mangunkusumo General Hospital
Jakarta Pusat, DKI Jakarta, Indonesia
Universitas Indonesia Hospital
Depok, West Java, Indonesia
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ismail H Dilogo, MD, PhD
Indonesia University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 27, 2020
First Posted
July 7, 2020
Study Start
July 1, 2020
Primary Completion
August 1, 2020
Study Completion
September 1, 2020
Last Updated
July 7, 2020
Record last verified: 2020-07