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Mesenchymal Stem Cell Therapy for SARS-CoV-2-related Acute Respiratory Distress Syndrome

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: NCT04366063
Recruitment Status : Recruiting
First Posted : April 28, 2020
Last Update Posted : April 30, 2020
Sponsor:
Collaborators:
Tehran University of Medical Sciences
Shahid Beheshti University of Medical Sciences
Information provided by (Responsible Party):
Royan Institute

Brief Summary:
Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed.

Condition or disease Intervention/treatment Phase
Covid-19 Biological: Cell therapy protocol 1 Biological: Cell therapy protocol 2 Phase 2 Phase 3

Detailed Description:

Acute respiratory distress syndrome (ARDS) is the major cause of death in the COVID 19 infection pandemic. It is a devastating clinical condition, caused by an acute and diffuse lung injury that requires management in the intensive care unit. It is caused by uncontrolled inflammation that leads to severe pulmonary alveolar damage and capillary membrane leakage, and progressive respiratory failure. There is no effective treatment for ARDS and the only supportive care strategies are the mainstay of therapy. Mesenchymal stem cells (MSCs) have high regenerative and immunomodulatory capacities. In preclinical research, ARDS, MSCs modulate the inflammatory response, augment tissue repair, enhance pathogen clearance, and reduce the severity of the injury, pulmonary dysfunction, and apoptosis. Moreover, many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus (e.g., Influenza)-induced lung injury and mortality in animals. Since 2014 clinical trials are using MSC from variable sources [bone marrow (BM), fat, and umbilical cord (UC)] in the treatment of ARDS. Some of the clinical trials are ongoing and the final reports are not reported. In all final reports, the safety of the application of MSC has been documented and most of them implied improvement in mortality and decrease of morbidity. Moreover, experimental studies have demonstrated that MSCs or their extracellular vesicles (MSCs-EVs) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. Also, macrophage phagocytosis, bacterial killing, and the outcome are improved. It is highly likely that MSCs-EVs have the same therapeutic effect on inoculation pneumonia as MSCs themselves.

Critically ill coronavirus documented cases suspicious to ARDS (mild or moderate) will be enrolled in the study. Our previous experiment (IRCT20200217046526N1) showed the safety of 3 injections of MSCs in patients with COVID-19. This multi-center trial will recruit 60 patients. All patients in all groups will receive conventional therapy for virus treatment and supportive care for ARDS.

The patients allocated randomly to three groups:

Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control.

Intervention Group1 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 intravenously.

Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 plus two doses of extracellular vesicles (EVs) on Day 4 and Day 6 intravenously.

The clinical symptoms, pulmonary imaging, side effects, 28-days mortality inflammatory factors, etc. will be evaluated during the 28 days follow up.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome in Coronavirus Infection: A Phase 2-3 Clinical Trial
Actual Study Start Date : April 5, 2020
Estimated Primary Completion Date : June 6, 2020
Estimated Study Completion Date : December 10, 2020


Arm Intervention/treatment
Experimental: Two MSC infusion
Intervention Group1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) intravenously plus Conventional treatment.
Biological: Cell therapy protocol 1
Cell therapy protocol 1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) at Day 0 and Day 2 plus Conventional treatment.

Experimental: Two MSC infusion Plus two EVs infusion
Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), intravenously plus two doses of EVs plus Conventional treatment
Biological: Cell therapy protocol 2
Patients will receive two doses of MSCs 100×10e6 (±10%)at Day 0 and Day 2, intravenously plus two doses of EVs at Day 4 and Day 6 plus conventional treatment.

No Intervention: Control
Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control.



Primary Outcome Measures :
  1. Adverse events assessment [ Time Frame: From baseline to day 28 ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2. Blood oxygen saturation [ Time Frame: From baseline to day 14 ]
    Evaluation of Pneumonia Improvement


Secondary Outcome Measures :
  1. Intensive care unit-free days [ Time Frame: Up to day 8 ]
    Number of days

  2. Clinical symptoms [ Time Frame: From baseline to day 14 ]
    Improvement of clinical symptoms including duration of fever, respiratory distress, pneumonia, cough, sneezing

  3. Respiratory efficacy [ Time Frame: From baseline to day 7 ]
    increase in PaO2/FiO2 ratio from baseline to day 7

  4. Biomarkers concentrations in plasma [ Time Frame: At baseline, 7, 14, 28 days after the first intervention ]
    Biochemical examination



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmation of 2019-nCoV infection by RT-PCR
  • Diagnosis of ARDS according to the Berlin definition of ARDS
  • Requiring supplemental oxygen
  • Pneumonia that is judged by chest radiograph or CT
  • PaO2/oxygen absorption concentration (FiO2) ≤ 300MMHG
  • Pulmonary imaging shows that the focused progress > 50% in 24-48 hours
  • Mild to Moderate 2019-nCoV pneumonia/ stay in the ICU <48 hours
  • SOFA score between 2-3 point

Exclusion Criteria:

  • Severe allergies or allergies after 1st injection to stem cell preparations and their components
  • Patients with a malignant tumor, other serious systemic diseases, and psychosis
  • Co-Infection of HIV, tuberculosis, influenza virus, adenovirus, and other respiratory infection viruses
  • Patients with a previous history of pulmonary embolism
  • Be thought by researchers to be inappropriate to participate in this clinical study (Expected deaths within 48 hours, uncontrolled infections)
  • Liver or kidney SOFA score of more than 3 points; combined with other organ failures (need organ support), Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30)
  • Pulmonary obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis, allergic alveolitis, and other known viral pneumonia or bacterial pneumonia
  • Continuous use of immunosuppressive agents or organ transplants in the past 6 months
  • In vitro life support (ECMO, ECCO2R, RRT)
  • Pregnant or lactating women
  • Uncontrolled underlying disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04366063


Contacts
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Contact: Masoumeh Nouri 00982127635512 masoume.nouri2002@gmail.com
Contact: Hoda Madani 00982122518388 hoda62_m@yahoo.com

Locations
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Iran, Islamic Republic of
Royan Institute Recruiting
Tehran, Iran, Islamic Republic of, 16635148
Contact: Masoumeh Nouri       masoume.nouri2002@gmail.com   
Contact: Hoda Madani       hoda62_m@yahoo.com   
Principal Investigator: Hossein Baharvand, Professor         
Sponsors and Collaborators
Royan Institute
Tehran University of Medical Sciences
Shahid Beheshti University of Medical Sciences
Investigators
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Study Chair: Abdol Hossein Shahverdi Royan Institute
Principal Investigator: Hossein Baharvand, Professor Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cells Biology & Technology, Iran
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Responsible Party: Royan Institute
ClinicalTrials.gov Identifier: NCT04366063    
Other Study ID Numbers: 991919
IRCT20200217046526N2 ( Registry Identifier: Iranian Registry of Clinical Trials (IRCT) )
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: April 30, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: 6 months after publication
Access Criteria: Researchers and clinicians

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Royan Institute:
COVID-19
Acute Respiratory Distress Syndrome
2019 Novel Coronavirus Pneumonia
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury