Clinical trial NCT04392778: Clinical Use of Stem Cells for the Treatment of Covid-19
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
Pneumonia
Multiple Organ Failure
Corona Virus Infection
Keywords: Covid-19
Pneumonia
Multiple Organ Failure
Coronavirus
Mesenchymal stem cells
Cellular therapy
Lead sponsor: SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Sponsor class: OTHER
Collaborators: name: Istinye University
name: Regenerative Medicine and Stem Cell Production Center Liv MedCell
name: Liv Hospital (Ulus)
First posted: 2020-05-19
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

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).

Eligibility criteria: 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

Primary outcomes:
measure: Clinical improvement
timeFrame: 3 months
Secondary outcomes:
measure: Lung damage improvement
timeFrame: 3 months
measure: Sars-Cov-2 viral infection laboratory test
timeFrame: 3 months
measure: Blood test
timeFrame: 3 months
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istinye University
city: Istanbul
country: Turkey
facility: SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Study officials:
affiliation: SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
name: Gokhan T Adas, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istinye University
name: Erdal Karaoz, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References: