Covid19Phase 1/2NCT04392778
Clinical Use of Stem Cells for the Treatment of Covid-19
A Phase 1/2 study testing MSC Treatment in people with Covid19 and Pneumonia, run by SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi at 2 sites in Turkey (Türkiye).
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 60 years
- Conditions the study is for
- Covid19, Pneumonia, Multiple Organ Failure
- What is being tested?
- MSC Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- 1 Apr 2020to 30 Nov 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 10Show fewer
- History of epilepsy and need for continuous anticonvulsant therapy or anticonvulsant therapy taken within 3 years;
- Invasive ventilation
- Shock
- Other organ failures
Trial locations and contacts
2 sites in 1 country.
Turkey (Türkiye)2 sites
Istinye University
Istanbul, 34010
SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Istanbul, 34147
About this study
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)
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.
Read the 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 ---------------------------------------- --------- 3. Day
- 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).
- Conditions
- Covid19, Pneumonia, Multiple Organ Failure, Corona Virus Infection
- Being tested
- MSC Treatment, Saline Control
- Keywords
- Covid-19, Pneumonia, Multiple Organ Failure, Coronavirus, Mesenchymal stem cells, Cellular therapy
- Medical subject headings
- COVID-19, Pneumonia, Multiple Organ Failure, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC TreatmentBiological
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.
Saline ControlBiological
Saline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.
| Study group | Role | What they receive |
|---|---|---|
| Untreated | No intervention | Group 1: patients that are not on a ventilator (n=10) No extra intervention will be done. |
| Saline Control | Sham comparator | Group 2: patients that are on a ventilator and will receive saline injections (n=10) as control for MSC transplantation group (3). Receives: Biological: Saline Control |
| Experimental UC-MSCs | Experimental | Group 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10) Receives: Biological: MSC Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical improvement
Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)
Measured: 3 months
Secondary outcomes (3)
Lung damage improvement
Improvement of lungs assessed by CT Scan
Measured: 3 months
Sars-Cov-2 viral infection laboratory test
Negative, measured by RT-PCR laboratory tests for the virus
Measured: 3 months
Blood test
Cell types and numbers
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start1 Apr 2020
- Primary completion1 Nov 2020
- Study completion30 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
- Sponsor type
- University, hospital or other
- Collaborators
- Istinye University, Regenerative Medicine and Stem Cell Production Center Liv MedCell, Liv Hospital (Ulus)
- Responsible party
- Sponsor
- Investigators
- Gokhan T Adas, Prof.Dr., Principal investigator, SBÜ Dr. Sadi Konuk Eğitim ve Araştırma HastanesiErdal Karaoz, Prof.Dr., Principal investigator, Istinye University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04392778
- Sponsor's protocol ID
- Bak. Sadi Konuk-Istinye Uni.
- Status last verified
- May 2020
- First submitted
- 25 Apr 2020
- Last updated
- 25 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04392778
- Acronym / sponsor ID
- Bak. Sadi Konuk-Istinye Uni.
- Conditions
- Covid19, Pneumonia, Multiple Organ Failure, Corona Virus Infection
- Keywords
- Covid-19, Pneumonia, Multiple Organ Failure, Coronavirus, Mesenchymal stem cells, Cellular therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- SBÜ Dr. Sadi Konuk Eğitim ve Araştırma HastanesiUniversity, hospital or other
- Collaborators
- Istinye University, Regenerative Medicine and Stem Cell Production Center Liv MedCell, Liv Hospital (Ulus)
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 1 Nov 2020 (actual)
- Study completion
- 30 Nov 2020 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 ---------------------------------------- --------- 3. Day
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Untreated | No intervention | –Group 1: patients that are not on a ventilator (n=10) No extra intervention will be done. |
| Saline Control | Sham comparator | Biological: Saline ControlGroup 2: patients that are on a ventilator and will receive saline injections (n=10) as control for MSC transplantation group (3). |
| Experimental UC-MSCs | Experimental | Biological: MSC TreatmentGroup 3: patients that are on a ventilator and will receive MSC transplantation injections (n=10) |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSC TreatmentProtocol 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 | Experimental UC-MSCs |
| Saline ControlSaline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation. | Biological | Saline Control |
Primary outcome
Clinical improvement
Time frame: 3 months
Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)
3 secondary outcomes
Lung damage improvement
Time frame: 3 months
Sars-Cov-2 viral infection laboratory test
Time frame: 3 months
Blood test
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Individual participant dataSharing planned: No
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gokhan T Adas, Prof.Dr. principal investigator
SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi
Erdal Karaoz, Prof.Dr. principal investigator
Istinye University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MSC Treatment in people with Covid19 and Pneumonia, run by SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi at 2 sites in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical improvement (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.