Clinical Use of Stem Cells for the Treatment of Covid-19
Ключови думи
Резюме
Описание
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:
1. 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,
2. Correcting immunosuppression in patients and increasing the fight against COVID-19 virus by CD4+T, CD+8T cellular cell arrangement,
3. 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:
1. Application: 3 million cells / kg IV ---------------------------------------- --------- 1 day
2. Application: 3 million cells / kg IV ---------------------------------------- --------- 3. Day
3. Application: 3 million cells / kg IV ---------------------------------------- --------- 6. 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).
Дати
Последна проверка: | 04/30/2020 |
Първо изпратено: | 04/24/2020 |
Очаквано записване подадено: | 05/16/2020 |
Първо публикувано: | 05/18/2020 |
Изпратена последна актуализация: | 05/16/2020 |
Последна актуализация публикувана: | 05/18/2020 |
Действителна начална дата на проучването: | 03/31/2020 |
Приблизителна дата на първично завършване: | 06/30/2020 |
Очаквана дата на завършване на проучването: | 08/31/2020 |
Състояние или заболяване
Интервенция / лечение
Biological: Experimental UC-MSCs
Biological: Saline Control
Фаза
Групи за ръце
Arm | Интервенция / лечение |
---|---|
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: Experimental UC-MSCs 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. |
Критерии за допустимост
Възрасти, отговарящи на условията за проучване | 40 Years Да се 40 Years |
Полове, допустими за проучване | All |
Приема здрави доброволци | Да |
Критерии | 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: 1. Shortness of breath (RR ≥30/min) 2. Resting finger oxygen saturation 93% 3. Arterial oxygen partial pressure (PaO2)/oxygen absorption concentration (FiO2) ≤ 300MMHG 4. 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 |
Резултат
Първични изходни мерки
1. Clinical improvement [3 months]
Вторични изходни мерки
1. Lung damage improvement [3 months]
2. Sars-Cov-2 viral infection laboratory test [3 months]
3. Blood test [3 months]