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Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia

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ClinicalTrials.gov Identifier: NCT04339660
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : April 9, 2020
Sponsor:
Collaborators:
Shanghai University
Qingdao Co-orient Watson Biotechnology group co. LTD
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Puren Hospital Affiliated to Wuhan University of Science and Technology

Tracking Information
First Submitted Date  ICMJE April 2, 2020
First Posted Date  ICMJE April 9, 2020
Last Update Posted Date April 9, 2020
Actual Study Start Date  ICMJE February 1, 2020
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2020)
  • The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP) [ Time Frame: Observe the immune function of the participants within 4 weeks ]
    Improvement and recovery time of inflammatory and immune factors
  • Blood oxygen saturation [ Time Frame: Monitor blood oxygen saturation of the participants within 4 weeks ]
    Evaluation of Pneumonia change
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2020)
  • Rate of mortality within 28-days [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Marker for efficacy of treatment
  • Size of lesion area by chest imaging [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Evaluation of Pneumonia change
  • CD4+ and CD8+ T cells count [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Marker of Immunology and inflammation
  • Peripheral blood count recovery time [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Degree of infection
  • Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.) [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Indirect response to lung function
  • COVID-19 nucleic acid negative time [ Time Frame: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4 ]
    Clearance time of COVID-19 in participant
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 Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia
Official Title  ICMJE Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia
Brief Summary The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Detailed Description

Since December 2019, novel coronavirus disease 2019 (COVID-19) in Wuhan has been fierce and spread rapidly. As of 24:00 on March 4, 2020, China has reported a total of 80567 confirmed cases, 5952 existing critically ill cases, and 3016 dead cases. The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the critically ill cases.

Recently, some clinical researches about the COVID-19 published in The Lancet and The New England Journal of Medicine suggested that massive inflammatory cell infiltration and inflammatory cytokines secretion were found in patients' lungs, alveolar epithelial cells and capillary endothelial cells were damaged, causing acute lung injury. Several reports demonstrated that the first step of the HCoV-19 pathogenesis is that the virus specifically recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike Protein. This receptor is abundant in lung and small intestinal tissues, but is also highly expressed in vascular endothelial cells and smooth muscle cells in almost all organs, including the nervous system and skeletal muscle. The main organ injured by the HCoV-19 is the lung. In fact, HCoV-19 can also involve the nervous system, digestive system, urinary system, blood system and other systems. Therefore, when the initial symptom is discomfort of other systems in the early stage, it is often easy to be misdiagnosed and delay treatment. Moreover, the HCoV-19 is a noncellular form consisting of RNA and protein, which cannot be copied independently. It needs to bind to cell surface receptors to enter the cell to complete the replication, and then be released again. Therefore, once the HCoV-19 enters the blood circulation, it can easily spread to all systems throughout the body, which may be the pathological mechanism that the HCoV-19 directly or indirectly causes neurological symptoms.

It seems that the key to cure the COVID-19 pneumonia is to inhibit the inflammatory response, resulting to reduce the damage of alveolar epithelial cells and endothelial cells and repair the function of the lung. MSCs, owing to their powerful immunomodulatory ability, may have beneficial effects on preventing or attenuating the cytokine storm.

Mesenchymal stem cells (MSCs) are widely used in basic research and clinical application. They are proved to migrate to damaged tissues, exert antiinflammatory and immunoregulatory functions, promote the regeneration of damaged tissues and inhibit tissue fibrosis. MSCs play a positive role mainly in two ways, namely immunomodulatory effects and differentiation abilities. MSCs can secrete many types of cytokines by paracrine secretion or make direct interactions with immune cells, leading to immunomodulation. Studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses by reducing the levels of proinflammatory cytokines and the recruitment of inflammatory cells into the lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (UC-MSCs) have been widely applied to various diseases due to their convenient collection, no ethical controversy, low immunogenicity, and rapid proliferation rate.

Here we conducted an MSC transplantation pilot study to explore their therapeutic potential for COVID-19 pneumonia patients. To explore the effective treatment of COVID-19 pneumonia for the current prevention and control of novel coronavirus pneumonia to find a key and effective clinical treatment means, to fight against the epidemic.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Biological: UC-MSCs
    1*10E6 UC-MSCs /kg body weight suspended in 100mL saline
  • Other: Placebo
    100mL saline intravenously
Study Arms  ICMJE
  • Experimental: UC-MSCs treatment group
    Participants will receive conventional and treatment with MSCs, MSCs were suspended in 100 mL of normal saline, and the total number of transplanted cells was calculated by 1*10E6 cells per kilogram of weight. This product is generally a course of treatment, a total of 1 time, depending on the condition of the need to be given again at an interval of 1 week.
    Intervention: Biological: UC-MSCs
  • Placebo Comparator: Control group
    Participants will receive conventional treatment and Placebo intravenously.
    Intervention: Other: Placebo
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: April 5, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, 18 years old ≤ age ≤ 75years old;
  2. CT image is characteristic of 2019 novel coronavirus pneumonia;
  3. Laboratory confirmation of 2019-nCoV infection by reverse transcription polymerase chain reaction (RT-PCR);
  4. In compliance with the 2019-nCoV pneumonia diagnosis standard (according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and WHO 2019 new coronavirus guidelines standards): (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
  5. Participant or the authorized agent signed the informed consent form.
  6. Agree to collect clinical samples.

Exclusion Criteria:

  1. Malignant disease in the past five years;
  2. Participant with no hope of survival were clinically predicted and only received hospice care, or those who were in a deep coma and did not respond to supportive treatment measures within three hours of admission.
  3. Participant who are participating in other clinical trials or who have participated in other clinical trials within 3 months.
  4. Cases of severe shock and respiratory failure.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yan Liu, MD +8613387517458 447822853@qq.com
Contact: Yue Zhu +8617786289703 978925651@qq.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04339660
Other Study ID Numbers  ICMJE Pr20200402
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 Not Provided
Responsible Party Puren Hospital Affiliated to Wuhan University of Science and Technology
Study Sponsor  ICMJE Puren Hospital Affiliated to Wuhan University of Science and Technology
Collaborators  ICMJE
  • Shanghai University
  • Qingdao Co-orient Watson Biotechnology group co. LTD
  • Chinese Academy of Medical Sciences
Investigators  ICMJE Not Provided
PRS Account Puren Hospital Affiliated to Wuhan University of Science and Technology
Verification Date April 2020

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