Clinical Use of Stem Cells for the Treatment of Covid-19

Sponsor

SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi (Other)

Overall Status

Completed

CT.gov ID

NCT04392778

Collaborator

Istinye University (Other), Regenerative Medicine and Stem Cell Production Center Liv MedCell (Other), Liv Hospital (Ulus) (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Pneumonia Multiple Organ Failure Corona Virus Infection	Biological: MSC Treatment Biological: Saline Control	Phase 1/Phase 2

Detailed Description

Introduction:

The COVID-19 corona virus epidemic has spread from Wuhan, China to the whole world, and has been declared a pandemic by WHO worldwide. In severe patients, ARDS and multiple organ failure can be seen. This condition is associated with cytokine storm in the body. When the virus invades the body, dentric cells can activate macrophages, lymphocytes and natural killer cells. Mesenchymal stem cells (MKH) not only inhibit the abnormal activation of T lymphocytes and macrophages, but also encourage them to differentiate into regulatory T cell subsets (Treg) clusters and anti-inflammatory macrophages. MSCs application proved therapeutic efficiency during influenza infection resulting in reduced impairment of alveolar fluid clearance and lung injury. This was attributed towards attenuation of pro-inflammatory cytokine secretion, inflammatory cell recruitment and increased alveolar macrophages content.

Aim of study:

To provide immune modulation to patients with COVID-19 who are taken to intensive care and resistant to treatment by performing MSCs transplantation and to reduce the damage caused by cytokin storm to tissues and organs,
Correcting immunosuppression in patients and increasing the fight against COVID-19 virus by CD4+T, CD+8T cellular cell arrangement,
It is to accelerate the recovery in organ damage by increasing growth factors by means of MSCs.

Materials and method:

Patients diagnosed with COVID-19 infection as clinically, radiologically and laboratory-wise will be divided into three groups:

Group 1: patients that are not on a ventilator (n=10) Group 2: patients that are on a ventilator and will receive saline injections (n=10) Group 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10)

Mesenchymal stem cells originating from allogenic umbilical cord produced under GMP conditions will be administered in 3 times, with doses indicated below, intravenously within 1 week.

Dose:

Application: 3 million cells / kg IV ---------------------------------------- --------- 1 day
Application: 3 million cells / kg IV ---------------------------------------- ---------
Day
Application: 3 million cells / kg IV ---------------------------------------- ---------
Day

The blood will be analyzed for the expression levels of growth factors, including vascular endothelial growth factor, fibroblast growth factor, platelet derived-growth factor, epidermal growth factor, transforming growth factor beta, hepatocyte growth factor, nerve growth factor, VEGF receptor (VEGFR), angiopoietin1 (Angpt-1), and Angpt-2, using sandwich enzyme-linked immune sorbent assays (ELISAs). Investigators also analyzed the caspase-3 system in the blood. immunoassay kits will be used for analyses in accordance with the manufacturer's instructions.

Biochemical parameters of the liver, such as alanine transaminase (ALT), aspartate transaminase (AST), total protein, albumin, total bilirubin, direct bilirubin, and alkaline phosphatase (ALP) levels, will be measured in the venous blood samples.

Proinflammatory (IL1-β, IL-6, TNFα, INF-γ) and anti-inflammatory (IL-2, IL-4, IL-10, IL-13) cytokines will be examined in venous blood in order to determine the immune modulatory effect of stem cells. CD4 + T, CD4 + T killer cells Granulocyte macrophage colony factor BLC-2 VEGF-R angiopoetin-1, angiopoetin-2 Total antioxidant capacity (TAC) Total oxidant capacity (TOC).

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

What is the Effect of Mesenchymal Stem Cell Therapy on Seriously Ill Patients With Covid 19 in Intensive Care? (Prospective Double Controlled Study)

Actual Study Start Date :

Apr 1, 2020

Actual Primary Completion Date :

Nov 1, 2020

Actual Study Completion Date :

Nov 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Untreated Group 1: patients that are not on a ventilator (n=10) No extra intervention will be done.
Sham Comparator: Saline Control Group 2: patients that are on a ventilator and will receive saline injections (n=10) as control for MSC transplantation group (3).	Biological: Saline Control Saline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.
Experimental: Experimental UC-MSCs Group 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10)	Biological: MSC Treatment Protocol length: 1 week Doses: Application: 3 million cells/kg IV-------------------------------------------------0 day Application: 3 million cells/kg IV ------------------------------------------------3rd day Application: 3 million cells/kg IV -------------------------------------------------6th day will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.

Arm

Intervention/Treatment

No Intervention: Untreated

Group 1: patients that are not on a ventilator (n=10) No extra intervention will be done.

Sham Comparator: Saline Control

Group 2: patients that are on a ventilator and will receive saline injections (n=10) as control for MSC transplantation group (3).

Biological: Saline Control

Saline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.

Experimental: Experimental UC-MSCs

Group 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10)

Biological: MSC Treatment

Protocol length: 1 week Doses: Application: 3 million cells/kg IV-------------------------------------------------0 day Application: 3 million cells/kg IV ------------------------------------------------3rd day Application: 3 million cells/kg IV -------------------------------------------------6th day will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.

Outcome Measures

Primary Outcome Measures

Clinical improvement [3 months]
Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)

Secondary Outcome Measures

Lung damage improvement [3 months]
Improvement of lungs assessed by CT Scan
Sars-Cov-2 viral infection laboratory test [3 months]
Negative, measured by RT-PCR laboratory tests for the virus
Blood test [3 months]
Cell types and numbers

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

40-60 years old male or female
Confirmed 2019-nCoV infection with RT-PCR Laboratory test
Confirmed Pneumonia with chest radiography and computer tomography
and any of the following criteria:

Shortness of breath (RR ≥30/min)
Resting finger oxygen saturation 93%
Arterial oxygen partial pressure (PaO2)/oxygen absorption concentration (FiO2) ≤ 300MMHG
Advancing of focus in Pulmonary imaging to >50% in 24-48 hours

Exclusion Criteria:

Those who are not pregnant, breastfeeding and pregnant but who do not take effective contraceptive measures;
Patients with malignant tumors, other serious systemic diseases and psychosis;
Informed consent is not given or does not comply with the test requirements.
Co-infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or co-infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
Obstructive HABP / VABP caused by lung cancer or other known causes; Long-term history of use of immunosuppressive agents;
History of epilepsy and need for continuous anticonvulsant therapy or anticonvulsant therapy taken within 3 years;
Invasive ventilation
Shock
Other organ failures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Istinye University	Istanbul		Turkey	34010
2	SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi	Istanbul		Turkey	34147

Sponsors and Collaborators

SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Istinye University
Regenerative Medicine and Stem Cell Production Center Liv MedCell
Liv Hospital (Ulus)

Investigators

Principal Investigator: Gokhan T Adas, Prof.Dr., SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Principal Investigator: Erdal Karaoz, Prof.Dr., Istinye University