Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection

The Application and Research of Mesenchymal Stem Cells in Alleviating the Severe Development of Novel Coronavirus Infection to Clarify Its Safety and Effectiveness.

This study is to evaluate the safety and efficacy of umbilical cord mesenchymal stem cells Therapy for COVID-19.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator

Detailed Description

Since 2019, novel coronavirus Disease 2019 (COVID-19) has spread and prevailed all over the world. COVID-19 has a wide range of clinical manifestations of respiratory and non-respiratory symptoms, including mild or severe influenza-like syndrome, respiratory distress or respiratory failure, and may end in multiple organ failure. Mesenchymal stem cells (MSCS) are considered as ideal seed cells for the treatment of various diseases due to their unique immune regulation, self-renewal and multiple differentiation potentials. The safety of MSC transplantation in the treatment of COVID-19 patients has been proved by a number of clinical studies, and has shown good clinical efficacy in shortening the course of the disease, alleviating lung damage, and reducing the level of inflammatory factors. However, previous clinical studies mainly focused on the efficacy of MSC transplantation in critically ill patients of COVID-19, ignoring the important role of cell transplantation in delaying or preventing COVID-19 's progress and preventing reinfection.COVID-19 has spread throughout the country and even the world, and the increase in severe and critical cases has caused a great impact on national medical and health resources. Stem cell transplantation offers new treatment ideas for COVID-19 patients. Since the role of cell transplantation in delaying or preventing the progression of light and medium novel coronavirus infection and preventing reinfection has not been clearly reported, this study intends to use MSC transplantation to evaluate the role of stem cells in the occurrence and development of novel coronavirus infection, so as to provide an important reference for the prevention and treatment of COVID-19 by MSC.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xianyun Wang, Doctor; Phone Number: 031187156290; Email: wangxianyun_mbb@126.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050030
      • Recruiting
      • The First Hospital of Hebei Medical University
      • Contact: Xianyun Wang, Doctor; Phone Number: 031187156290; Email: wangxianyun_mbb@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-85 years;The diagnosis of COVID-19 infection was clinically classified as Moderate cases, and the criteria were based on Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia(Trial Version 10)
• Having the relevant clinical manifestations of COVID-19 infection.
• Having one or more of the following etiological and serological examination results
• Tested positive for Novel Coronavirus nucleic acid
• Tested positive for Novel Coronavirus antigen
• Novel Coronavirus was isolated and cultured positive
• Novel Coronavirus specific immunoglobulin G reaches a titration of at least 4-fold increase during convalescence compared with the acute phase.
• Moderate cases diagnostic criteria：Persistent high fever > 3 days or (and) cough, Tachypnea etc，but respiratory rate≧30 breaths/ min ,oxygen saturation > 93% on finger pulse oximeter taken at rest. Radiology shows the characteristic manifestations of COVID-19 pneumonia
• There are one or more of the following risk factors for the development of severe / critical severity:
• Patients over 65 years old, especially those who have not been vaccinated against novel coronavirus
• Patients with cardiovascular and cerebrovascular diseases (including hypertension), chronic lung disease, diabetes, chronic liver and kidney disease, tumors and other underlying diseases, as well as maintenance dialysis
• Patients with immune deficiency (such as AIDS, long-term use of corticosteroids or other immunosuppressive drugs resulting in immune dysfunction)
• Patients with Obesity (body mass index ≥30)
• late trimester of pregnancy and perinatal women
• Heavy smoker.

Exclusion Criteria:

• Patients with prior or present tumor history,or precancerous lesions confirmed by pathological examination.
• Patients with active acute myocardial infarction or acute cerebral infarction.
• Pregnant or lactating patients.
• Patients with poorly controlled mental illness.
• Patients addicted to alcohol or drugs.
• Patients Unable or unwilling to sign informed consent or poor compliance.
• Patients with active tuberculosis or influenza virus, adenovirus and other acute respiratory virus infection.
• Patients deemed unsuitable for stem cell therapy by clinicians.
• Patients enrolled in other clinical trials within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSCs group; Patient in Mscs group will receive MSCs implantation by intravenous injection Within 10-15 days of infection	Biological: Umbilical cord mesenchymal stem cells implantation; Patient in Mscs group will receive MSCs implantation by intravenous injection.
Placebo Comparator: comparator; Patients in comparator group will receive placebo treatment Within 10-15 days of infection	Other: Comparator; Patients in comparator group will receive placebo treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness evaluation	The incidence and clinical status of progression to critical type after the third stem cell transplantation were evaluated	Within 1 year of receiving mesenchymal stem cell transplants

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization time	The patient's hospital stay in days should be recorded.	Time period from patient admission to discharge
oxygenation index（OI）	The oxygenation index of the patient was quantitatively measured in mmHg.	At the time of our patient's hospitalization and 7 days after receiving the third MSC transplant.
Oxygen saturation（SaO2）	The blood oxygen saturation of patients was monitored by oximeter.	At the time of our patient's hospitalization and 7 days after receiving the third MSC transplant.
Chest CT	A computed tomography (CT) scan of the patient's chest was performed to evaluate the level of inflammation, the scope of the involvement, and the degree of fibrosis in the heart and lungs.	At admission, before to the stem cell transplant, and at 1 month, 6 months, and 12 months following the third MSC transplant.
Pulmonary function evaluation	Lung ventilation experiments were used to measure the lung volume (in ml) and airway patency (in ml) of patients in order to assess their lung function.	At admission, before to the stem cell transplant, and at 1 month, 6 months, and 12 months following the third MSC transplant.
Blood biochemical examination	The progression of the lesion was determined by blood chemistry tests on a patient's blood sample, which mostly included liver function: Alanine aminotransferase (U/L)，Glutamic oxaloacetic transaminase (U/L), renal function:blood urea nitrogen (mmol/L) and serum creatinine (umol/L), cardiac function: creatine kinase isoenzymes(U/L) and Troponin(ng/ml), and inflammatory factors: C- reactive protein (mg/dl) and Interleukin- 6(Pg/ml) .	At admission, before to the stem cell transplant, and at 1 month, 6 months, and 12 months following the third MSC transplant.
Echocardiographic examination of heart function	Echocardiography was used to evaluate the patient's myocardial contractility, primarily focusing on left ventricular ejection fraction (LVEF).	At admission, before to the stem cell transplant, and at 1 month, 6 months, and 12 months following the third MSC transplant.
Safety assessment	infusion and allergic reactions, life-threatening adverse events	Within 1 year of receiving mesenchymal stem cell transplants

Collaborators and Investigators

• Sponsor: Hebei Medical University
• Investigators: Principal Investigator: Xianyun Wang, Doctor, The First Hospital of Hebei Medical University; Study Chair: Xifeng Jiang, Doctor, The First Hospital of Hebei Medical University; Study Director: Gang Liu, Master, The First Hospital of Hebei Medical University; Study Director: Wuzhuang Sun, Master, The First Hospital of Hebei Medical University; Principal Investigator: Baoyong Yan, Master, The First Hospital of Hebei Medical University; Principal Investigator: Mingqi Zheng, Master, The First Hospital of Hebei Medical University; Principal Investigator: Ding Yu, Master, The First Hospital of Hebei Medical University; Principal Investigator: Le Wang, Master, The First Hospital of Hebei Medical University; Principal Investigator: Yajie Wang, Master, The First Hospital of Hebei Medical University; Principal Investigator: Quanhai Li, Master, The First Hospital of Hebei Medical University; Principal Investigator: Jiawei Yang, Postgraduate, The First Hospital of Hebei Medical University; Principal Investigator: Tianshuo Li, Postgraduate, The First Hospital of Hebei Medical University

Publications and helpful links

General Publications

• Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020 Feb 15;395(10223):470-473. doi: 10.1016/S0140-6736(20)30185-9. Epub 2020 Jan 24. No abstract available. Erratum In: Lancet. 2020 Jan 29;:
• Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr.
• Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment. N Engl J Med. 2020 Feb 20;382(8):692-694. doi: 10.1056/NEJMp2000929. Epub 2020 Jan 24. No abstract available.
• Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available. Erratum In: Lancet Respir Med. 2020 Feb 25;:
• Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018 Jun 1;22(6):824-833. doi: 10.1016/j.stem.2018.05.004.
• Hashemian SR, Aliannejad R, Zarrabi M, Soleimani M, Vosough M, Hosseini SE, Hossieni H, Keshel SH, Naderpour Z, Hajizadeh-Saffar E, Shajareh E, Jamaati H, Soufi-Zomorrod M, Khavandgar N, Alemi H, Karimi A, Pak N, Rouzbahani NH, Nouri M, Sorouri M, Kashani L, Madani H, Aghdami N, Vasei M, Baharvand H. Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem Cell Res Ther. 2021 Jan 29;12(1):91. doi: 10.1186/s13287-021-02165-4.
• Zanirati G, Provenzi L, Libermann LL, Bizotto SC, Ghilardi IM, Marinowic DR, Shetty AK, Da Costa JC. Stem cell-based therapy for COVID-19 and ARDS: a systematic review. NPJ Regen Med. 2021 Nov 8;6(1):73. doi: 10.1038/s41536-021-00181-9.
• Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014 Nov;15(11):1009-16. doi: 10.1038/ni.3002.
• Shu L, Niu C, Li R, Huang T, Wang Y, Huang M, Ji N, Zheng Y, Chen X, Shi L, Wu M, Deng K, Wei J, Wang X, Cao Y, Yan J, Feng G. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther. 2020 Aug 18;11(1):361. doi: 10.1186/s13287-020-01875-5.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; MSC
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 2023-MSCs-COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No