Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19
|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: NCT04273646|
Recruitment Status : Not yet recruiting
First Posted : February 18, 2020
Last Update Posted : April 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|2019 Novel Coronavirus Pneumonia COVID-19||Biological: UC-MSCs Drug: Placebo||Not Applicable|
Since December 2019, Wuhan has successively found multiple cases of patients with pneumonia infected by a novel coronavirus. With the spread of the epidemic, other cases in China and abroad have also found such cases. As of 24:00 on February 1, 2020, a total of 14,380 confirmed cases were reported in China, of which there were 2110 severe cases and 304 death cases. At present, there is no effective treatment for pneumonia in the clinic against new coronavirus infection, especially severe and critical cases. Therefore, it is of great significance to explore more active and effective therapeutic approach to severe pneumonia patients infected with 2019-nCoV.
Human and animal studies have shown that after infection with coronavirus, the rapid replication of the virus in the body and the subsequent inflammatory response cause damage to alveolar epithelial cells and capillary endothelial cells, causing diffuse interstitial and alveolar edema, and pulmonary function. Impaired, leading to acute hypoxic respiratory insufficiency. The National Health and Medical Commission recently released the "New Coronavirus Infected Pneumonia Diagnosis and Treatment Plan (Trial Version 5)", which pointed out that the new type of coronavirus severe pneumonia usually has difficulty breathing after one week, and the severe cases quickly progress to acute respiratory distress syndrome, Septic shock and metabolic acidosis that is difficult to correct. It can be seen that the key to the treatment of new coronavirus severe pneumonia is to inhibit the super-inflammatory immune response caused by the virus, thereby reducing the damage of alveolar epithelial cells and capillary endothelial cells, and then repairing the structure and function of lung tissue.
Mesenchymal stem cells (MSCs) are one of the most studied and important adult stem cells. A large amount of evidence shows that MSCs can migrate to and return to damaged tissues, exert strong anti-inflammatory and immune regulatory functions, promote the regeneration and repair of damaged tissues, resist apoptosis and inhibit tissue fibrosis, and reduce tissue damage. Many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus-induced lung injury and mortality in mice. 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 chemokines and reducing the recruitment of inflammatory cells into the lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (umbilical cord MSCs, UC-MSCs) have been widely used because of their convenient collection, no ethical controversy, low immunogenicity, fast self-renewal and strong proliferation ability Research on the treatment of various diseases. Early research in this laboratory used UC-MSCs to intervene in endotoxin (LPS) -induced acute lung injury in mice, and confirmed that UC-MSCs can significantly reduce inflammatory cell infiltration in lung tissue, reduce inflammation in lung tissue, and significantly improve lung The structure and function of tissues protect mouse lung tissue from endotoxin-induced damage.
The purpose of this study is to investigate efficiency and safety of UC-MSCs in treating severe pneumonia patients infected with 2019-nCoV. This trial will recruit 48 patients. 24 patients received i.v. transfusion one round (4 times) of 5.0*10E6 cells/kg of UC-MSCs as the treated group, all of them received the conventional treatment. In addition, the equal 24 patients received conventional treatment were used as control group. The respiratory function, pulmonary inflammation, clinical symptoms, pulmonary imaging, side effects, 28-days mortality, immunological characteristics (immune cells, inflammatory factors, etc.) will be evaluated during the 90 days to 96 weeks follow up.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19|
|Estimated Study Start Date :||April 20, 2020|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||February 15, 2022|
Experimental: UC-MSCs Treatment Group
Conventional treatment plus UC-MSCs:
Participants will receive conventional treatment plus 4 times of UC-MSCs(0.5*10E6 UC-MSCs/kg body weight intravenously at Day 1，Day 3，Day 5，Day7).
4 times of UC-MSCs(0.5*10E6 UC-MSCs/kg body weight intravenously at Day 1, Day 3, Day 5, Day 7).
Placebo Comparator: Conventional Control Group
Conventional treatment plus Placebo:
Without UC-MSCs Therapy but conventional treatment should be received. Participants will receive conventional treatment plus 4 times of Placebo intravenously at Day 1，Day 3，Day 5，Day7).
4 times of cell-free stem cell suspension (saline containing 1% human albumin) intravenously at Day 1, Day 3, Day 5, Day 7).
- Pneumonia severity index [ Time Frame: From Baseline (0W) to 12 week after treatment ]Evaluation of Pneumonia Improvement
- Oxygenation index (PaO2/FiO2) [ Time Frame: From Baseline (0W) to 12 week after treatment ]Evaluation of Pneumonia Improvement
- Side effects in the UC-MSCs treatment group [ Time Frame: From Baseline (0W) to 96 week after treatment ]Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.
- 28-days survival [ Time Frame: Day 28 ]Marker for efficacy of treatment
- Sequential organ failure assessment [ Time Frame: Day 28 ]Markers of organ function（Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.）
- C-reactive protein [ Time Frame: From Baseline (0W) to 12 week after treatment ]Markers of Infection
- Procalcitonin [ Time Frame: From Baseline (0W) to 12 week after treatment ]Markers of Infection
- Lymphocyte count [ Time Frame: From Baseline (0W) to 12 week after treatment ]Marker of Immunological function
- CD3+, CD4+ and CD8+ T celll count [ Time Frame: From Baseline (0W) to 12 week after treatment ]Marker of Immunological function
- CD4+/CD8+ratio [ Time Frame: From Baseline (0W) to 12 week after treatment ]Marker of Immunological function
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): NCT04273646
|Contact: Yang Jin, MDfirstname.lastname@example.org|
|Contact: Yang Jin, MDemail@example.com|
|Union Hospital, Tongji Medical College, Huazhong University of Science and Technology|
|Wuhan, Hubei, China, 430000|