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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04392778
Recruitment Status : Recruiting
First Posted : May 19, 2020
Last Update Posted : May 19, 2020
Sponsor:
Collaborators:
Istinye University
Regenerative Medicine and Stem Cell Production Center Liv MedCell
Liv Hospital (Ulus)
Information provided by (Responsible Party):
SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi

Tracking Information
First Submitted Date  ICMJE April 25, 2020
First Posted Date  ICMJE May 19, 2020
Last Update Posted Date May 19, 2020
Actual Study Start Date  ICMJE April 1, 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2020)
Clinical improvement [ Time Frame: 3 months ]
Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2020)
  • Lung damage improvement [ Time Frame: 3 months ]
    Improvement of lungs assessed by CT Scan
  • Sars-Cov-2 viral infection laboratory test [ Time Frame: 3 months ]
    Negative, measured by RT-PCR laboratory tests for the virus
  • Blood test [ Time Frame: 3 months ]
    Cell types and numbers
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Use of Stem Cells for the Treatment of Covid-19
Official Title  ICMJE What is the Effect of Mesenchymal Stem Cell Therapy on Seriously Ill Patients With Covid 19 in Intensive Care? (Prospective Double Controlled Study)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • Pneumonia
  • Multiple Organ Failure
  • Corona Virus Infection
Intervention  ICMJE
  • Biological: MSC Treatment

    Protocol length: 1 week

    Doses:

    1. Application: 3 million cells/kg IV-------------------------------------------------0 day
    2. Application: 3 million cells/kg IV ------------------------------------------------3rd day
    3. 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.

  • Biological: Saline Control
    Saline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.
Study Arms  ICMJE
  • 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).
    Intervention: Biological: Saline Control
  • Experimental: Experimental UC-MSCs
    Group 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10)
    Intervention: Biological: MSC Treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gokhan T Adas, Prof.Dr. 05326155892 gokhantolgaadas@gmail.com
Contact: Erdal Karaoz, Prof.Dr. 05327423472 ekaraoz@hotmail.com
Listed Location Countries  ICMJE Turkey
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04392778
Other Study ID Numbers  ICMJE Bak. Sadi Konuk-Istinye Uni.
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Study Sponsor  ICMJE SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Collaborators  ICMJE
  • Istinye University
  • Regenerative Medicine and Stem Cell Production Center Liv MedCell
  • Liv Hospital (Ulus)
Investigators  ICMJE
Principal Investigator: Gokhan T Adas, Prof.Dr. SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Principal Investigator: Erdal Karaoz, Prof.Dr. Istinye University
PRS Account SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP