A Proof of Concept Study for the DNA Repair Driven by the Mesenchymal Stem Cells in Critical COVID-19 Patients

Study Overview
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Brief Summary
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Our aim in this study is to determine the positive effect of stem cell therapy applied on critically ill patients with coronavirus infection on DNA repair genes. Patients diagnosed with COVID-19 infection are divided into two equal (n:30) groups. Group-1(n/15): Patients in critically ill condition receiving conventional therapy, Group-2 (n/15): Patients in critically ill condition receiving conventional therapy and systemically transplanted MSCs. The DNA repair pathway will be examined as 11 genes in 5 different parts. Investigated parameters: Base excision repair Nucleotide excision repair Recombinational repair Mismatch repair Direct reversal Investigated parameters: broad biochemical analysis, apoptosis, clinical outcome, and mortality rates.

Detailed Description
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Our aim in this study is to determine the positive effect of stem cell therapy applied on critically ill patients with coronavirus infection on DNA repair genes. Patients diagnosed with COVID-19 infection are divided into two equal (n:30) groups. Group-1(n/15): Patients in critically ill condition receiving conventional therapy, Group-2 (n/15): Patients in critically ill condition receiving conventional therapy and systemically transplanted MSCs. The DNA repair pathway will be examined as 11 genes in 5 different parts. Investigated parameters: Base excision repair Nucleotide excision repair Recombinational repair Mismatch repair Direct reversal Investigated parameters: broad biochemical analysis, apoptosis, clinical outcome, and mortality rates.

Official Title
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A Proof of Concept Study for the DNA Repair Driven by the Mesenchymal Stem Cells in Critical COVID-19 Patients

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Biological: Mesenchymal Stem Cells Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40-65 years old male/female. Obtaining informed consent from him or his legal relative. Confirmed COVID-19 related severe ARDS cases. Exclusion Criteria: pregnant, malignant tumours, the ones who has confirmed co-infection; history of using long-term immunosuppressive agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional Therapy<br> | Biological: Mesenchymal Stem Cells Transplantation<br>* Mesenchymal Stem Cells Transplantation applied as three intravenous infusions with 30 days intervals<br>|
| Experimental: Conventional Therapy with Add-On MSC therapy<br> | Biological: Mesenchymal Stem Cells Transplantation<br>* Mesenchymal Stem Cells Transplantation applied as three intravenous infusions with 30 days intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of PARP1 gene as indicator of base excision repair | Expression of PARP1 gene as indicator of base excision repair | 6 months | 
| Expression of genes ATM, RAD51, RAD52 and WRN as indicator of Recombinational repair | Expression of genes ATM, RAD51, RAD52 and WRN as indicator of Recombinational repair | 6 months | 
| Expression of genes RAD23B and ERCC1 as indicator of Nucleotide excision repair | Expression of genes RAD23B and ERCC1as indicator of Nucleotide excision repair | 6 months | 
| Expression of genes MLH1, MSH2 and MSH6as indicator of Mismatch repair | Expression of genes MLH1, MSH2 and MSH6 as indicator of Mismatch repair | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Critical Case, DNA Repair, DAN damage