Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 Patients

Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe Pneumonia of COVID-19：a Single-center, Prospective, Randomised Clinical Trial

This clinical trial is set out to evaluate the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19; to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC); Other: Intravenous saline injection (Placebo)

Detailed Description

This clinical trial is set out to evaluate the followings:

1. the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19;
2. to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and
3. to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

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

Contacts and Locations

• Study Contact: Name: Qingsong Ye, PhD,DDS; Phone Number: +8615858242516; Email: qingsongye@foxmail.com
• Study Contact Backup: Name: Chenliang Zhou, PhD; Phone Number: 83920 +862788041919

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Renmin Hospital of Wuhan University (East Campus)
      • Contact: Chenliang Zhou, PhD; Phone Number: 83920 +86 027 88041919

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-65 years;
2. Voluntarily participate in this clinical trial and sign off "informed consent form";
3. Diagnosed with severe pneumonia of COVID: respiratory distress, RR >30 times / min; resting oxygen saturation of 93% or less; arterial partial pressure of oxygen / oxygen concentration 300mmHg; SARS-CoV-2 nucleic acid test was positive.
4. Chest imaging confirm COVID-19 featured lesions in lung.

Exclusion Criteria:

1. Receive any clinical trial drug treatment for COVID-2019 within 30 days before the screening assessment;
2. Severe liver disease (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);
3. Patients with known severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;
4. Co-infection of HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;
5. Female patients who have no sexual protection in the last 30 days prior to the screening assessment;
6. Pregnant or lactating women or women using estrogen contraception;
7. Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;
8. Other conditions that the researchers consider not suitable for participating in this clinical trial.

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: hDPSCs group; Routine treatment + Intravenous injection of human dental pulp stem cells	Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC); Intravenous injection of 3.0x10e7 human dental pulp stem cells solution (30ml) on day 1, day 4 and day 7, based on routine treatment of COVID-19
Placebo Comparator: Control group; Routine treatment + Intravenous saline injection (Placebo)	Other: Intravenous saline injection (Placebo); Intravenous injection of 3ml of 0.9% saline on day 1, day 4 and day 7, based on routine treatment of COVID-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTCI	Time to Clinical Improvement	1-28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung lesion	Lung Lesion by CT	1-28 days
Immune function	Th1 cytokines: IL-1β, IL- 2, TNF-a, ITN-γ;; Th2 cytokines: IL- 4, IL- 6, IL- 10;; Immunoglobulins: IgA, IgG, IgM, and total IgE;; Lymphocyte counts: CD3+, CD4+, CD8+, CD16+,CD19+, CD56+.	1-28 days
Time of SARS-CoV-2 clearance	Time of SARS-CoV-2 test turns negative	1-28 days
Blood test	Blood cell count and classification	1-28 days
SPO2	Pulse oximetry	1-28 days
RR	Respiratory rate	1-28 days
Body temperature	Body temperature	1-28 days
Side effects in the treatment group	Number of the included patients with hDPSCs-related adverse events, e.g. liver or kidney function failure	1-28 days
C-reactive protein (mg/L)	C-reactive protein in microgram per litre	1-28 days

Collaborators and Investigators

• Sponsor: Renmin Hospital of Wuhan University
• Collaborators: Beijing SH Bio-Tech Corporation, Beijing (CN); Utooth Biological Technology Co., Ltd. Hubei (CN)
• Investigators: Study Chair: Prof. Qingsong Ye, PhD,DDS, Center for Regenerative Medicine, Renmin Hospital of Wuhan University

Publications and helpful links

General Publications

• Ye Q, Wang H, Xia X, Zhou C, Liu Z, Xia ZE, Zhang Z, Zhao Y, Yehenala J, Wang S, Zhou G, Hu K, Wu B, Wu CT, Wang S, He Y. Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II). Trials. 2020 Jun 12;21(1):520. doi: 10.1186/s13063-020-04380-5.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: March 28, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (Actual): April 7, 2020

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Cronovirus; Human Dental Pulp Stem Cells; Dental Stem Cell Banking
• 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: 2020K-G005; hDPSC-CoVID-2019-02-2020 (Other Identifier: Renmin Hospital of Wuhan University)

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