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Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonian

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: NCT04282928
Recruitment Status : Not yet recruiting
First Posted : February 25, 2020
Last Update Posted : February 25, 2020
Sponsor:
Information provided by (Responsible Party):
Shanghai East Hospital

Tracking Information
First Submitted Date  ICMJE February 13, 2020
First Posted Date  ICMJE February 25, 2020
Last Update Posted Date February 25, 2020
Estimated Study Start Date  ICMJE February 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2020)
  • mortality [ Time Frame: 90 day ]
    The difference of 90 day mortality between the two groups will be observed and recorded
  • average length of stay [ Time Frame: 90 day ]
    The difference of average length of stay between the two groups will be observed and recorded
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2020)
  • Changes of inflammatory index - the number of leukocyte or lymphocyte [ Time Frame: Day 0, Day 1,Day 3,Day 7,Day 14,Day 30,Day 60,Day 90 ]
    Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood of the patients will be collected to detect the number of leukocyte (10^9/L) or lymphocyte (10^9/L).
  • Changes of inflammatory index - the percentage of lymphocytes [ Time Frame: Day 0, Day 1,Day 3,Day 7,Day 14,Day 30,Day 60,Day 90 ]
    Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood of the patients will be collected to detect the percentage of lymphocytes(%).
  • Changes of inflammatory index - cytokines [ Time Frame: Day 0, Day 1,Day 3,Day 7,Day 14,Day 30,Day 60,Day 90 ]
    Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the peripheral blood serum of the patients will be collected to detect the level of CRP, SAA, ESR, PCT and IL-6 (μg/L).
  • Changes of oxygenation index [ Time Frame: Day 0, Day 1,Day 3,Day 7,Day 14,Day 30,Day 60,Day 90 ]
    Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th day after the infusion, the arterial blood of the patients will be analyzed and the oxygenation index (mmHg) will be calculated according to the oxygen concentration of the patients. The change trend of the oxygenation index will be observed.
  • Throat swab/blood viral load [ Time Frame: Day 0, Day 1,Day 3,Day 7,Day 14,Day 30,Day 60,Day 90 ]
    Before the infusion of UC MSCs and on the 1st, 3rd, 7th, 14th, 30th, 60th and 90th days after the infusion, the throat swabs and peripheral blood were collected respectively. The RNA copies of the virus will be detected by RT-PCR. The change trend of the viral load in the throat swabs/peripheral blood of the patients in each group will be observed after the treatment with different regimens, and the difference of the viral load between different groups will be compared
  • Chest imaging outcome [ Time Frame: Day 0, Day 7, Day 30, Day 90 ]
    Two senior (associate chief physician and above) respiratory radiologists read the films independently. The chest CT images of the two groups will be evaluated before UC-MSCs infusion and on the 7th, 30th and 90th day after UC MSCs infusion. The changes of chest CT images at different time points before and after treatment will be observed and the differences between different treatment groups will be compared.
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 Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonian
Official Title  ICMJE A Singlecenter, Randomized, Open Lable, Intervention Controlled Clinical Study on the Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Viral Pneumonia
Brief Summary

The purpose of this clinical study is to answer the questions:

  1. Is the proposed intervention safe?
  2. Is the proposed intervention effective in improving the health of subjects with severe viral pneumonia?
Detailed Description

Viral pneumonia is an acute respiratory infectious disease caused by respiratory viruses. It is mainly caused by the invasion of respiratory viruses such as influenza virus and adenovirus into the lower respiratory tract. Every winter and spring is the epidemic season. Influenza virus and adenovirus have high infectivity and pathogenicity. The rapid progress of some patients may be caused by acute respiratory distress syndrome (ARDS) or multiple organ dysfunction And died of complications. The fatality rate of severe patients is 9.8% - 60%. Most of the dead cases were the elderly and the patients with basic diseases. In addition to the complications, the main cause of death is ARDS caused by virus infection, on the other hand, the basic immune function of the elderly is poor, so it is difficult to form an effective antiviral response in response to virus infection. The direct destruction of the alveolar epithelial barrier and the systemic inflammatory response induced by the infection, namely, the destruction of the alveolar capillary barrier by the inflammatory waterfall, are the important pathogenesis of ARDS. How to effectively regulate the inflammatory response, prevent the inflammatory exudation and edema of the lungs, improve oxygenation, and reduce organ damage; at the same time, how to effectively improve the basic immune function and enhance the anti-virus immune response of such patients, has become the key to the success of the treatment of patients with severe viral pneumonia.

Umbilical cord mesenchymal stem cells (UC-MSCs) can differentiate into the different germ layers and play an important role in immune regulation and damage repair regulation. Clinical trials have shown that MSC is safe and effective in the treatment of acute lung injury and pulmonary fibrosis, and it can improve the immune function of patients with viral infectious diseases. Hence, intravenous infusion of HUC-MSCs is attractive therapy against severe viral pneumonia.

This is a randomized, singlecenter, open lable, intervention controlled clinical trial. The participants (n = 40) will be randomly distributed into two groups. The routine treatment group (n = 20) will receive the treatment according to "Influenza diagnosis and treatment plan (2019 version)", the HUC-MSCs adjuvant Group (n = 20) will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment once at day 1 after joining. Follow-up duration is 90 days. The difference of 90 day mortality and average length of stay between the two groups will be observed and recorded. The changes of inflammatory index, viral load, oxygenation index and pulmonary imaging will be monitored at different time points after treatment in the two groups. The serious adverse events (SAEs) and adverse events (AEs) will be observed during the period.

The intent of this study is to explore the efficacy of HUC-MSCs in the treatment of severe viral pneumonia through improving the antiviral immune response of patients, reduce the lung inflammatory damage caused by the virus and the pulmonary interstitial fibrosis after the injury, and finally achieve the goal of reducing the mortality and improving the prognosis of severe patients, and to evaluate the safety.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Severe Pneumonia
Intervention  ICMJE
  • Biological: Human umbilical cord mesenchymal stem cells
    Definitive Human umbilical cord mesenchymal stem cells selected by immunomodulatory assay through coculture with BV2 cell
  • Procedure: Routine treatment
    According to"Influenza diagnosis and treatment plan (2019 version)"
Study Arms  ICMJE
  • Active Comparator: Routine treatment group
    Participants will receive the treatment according to the treatment principle of severe and critical cases in "Influenza diagnosis and treatment plan (2019 version)"
    Intervention: Procedure: Routine treatment
  • Experimental: HUC-MSCs adjuvant Group
    Participants will receive intravenous infusion of definitive HUC-MSCs (1×10^6 cells/Kg × body weight(kg), which was selected by immunomodulatory assay through coculture with BV2 cell) on the basis of the routine treatment.
    Interventions:
    • Biological: Human umbilical cord mesenchymal stem cells
    • Procedure: Routine 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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 21, 2020)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The age is 18-75 years old (inclusive), and the gender is not limited;
  2. According to the diagnosis standard of viral pneumonia in the influenza diagnosis and treatment plan (2019 version), patients with severe viral pneumonia were diagnosed.
  3. Diagnostic criteria of viral pneumonia: with clinical manifestations of influenza, with one or more of the following pathogenic test results positive: 1) influenza virus nucleic acid test positive. 2) influenza antigen was positive. 3) the culture of influenza virus was positive. 4) the level of influenza virus specific IgG antibody in the acute and recovery serum was 4 times or more higher. Diagnosis criteria of severe viral pneumonia: the confirmed patients meet any of the following criteria: 1) continuous high fever for more than 3 days, accompanied by severe cough, expectoration, blood sputum, or chest pain; 2) rapid respiratory rate, dyspnea, cyanosis of mouth and lips; 3) mental changes: slow response, drowsiness, agitation, convulsion, etc.; 4) severe vomiting, diarrhea, dehydration; 5) pneumonia; 6 )7. Other clinical conditions requiring hospitalization
  4. 20kg / m2 ≤ BMI ≤ 30 kg / m2;
  5. Volunteer to participate in the clinical study and sign the written informed consent.

Exclusion Criteria:

  1. Long term use of immunosuppressive drugs or organ transplantation;
  2. T lymphocyte abnormality (the use of allogeneic may be considered, according to the clinical opinion), HIV positive;
  3. High allergic constitution or severe allergic history, especially IL-2 allergic history;
  4. Pregnant and lactating women;
  5. Patients with a history of serious autoimmune diseases; those who are allergic to all biological agents in the treatment, such as IL-2;
  6. Patients with serious complications: Patients with chronic cardiac insufficiency (NYHA cardiac function grade IV), chronic renal insufficiency (CKD stage 4 or above), chronic liver insufficiency (child Pugh score > 12), and patients with malignant tumors.
  7. There are other situations that the researcher thinks are not suitable for participating in this clinical study.
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: Qiang Li, MD/Ph.D (+86)-13801602220 liqressh@hotmail.com
Contact: Zhongmin Liu, MD/Ph.D (+86)-21-38804518 liu.zhongmin@tongji.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04282928
Other Study ID Numbers  ICMJE EC.D(BG).013.02.0
Has Data Monitoring Committee Not Provided
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 Shanghai East Hospital
Study Sponsor  ICMJE Shanghai East Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zhongmin Liu, MD/Ph.D Shanghai East Hospital, Tongji University, Shanghai, China
PRS Account Shanghai East Hospital
Verification Date February 2020

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