Evaluation of the Safety and Efficiency of human Umbilical Cord Derived Mesenchymal Stem Cell Exosomes in patients with ARDS of COVID-19; An interventional randomized double-blind controlled clinical trial: phase I and II
The use of mesenchymal stem cells-derived exosomes that were cultured in an inflammatory niche, can have beneficial effects in preventing or reducing cytokine storms due to the high modulating potential of the immune system, and reduce the complications and mortality of this disease.
Design
A controlled trial with parallel groups, double-blind, randomized, phases 1 and 2 on 72 patients. The random sequence table was used to randomize the blocks.
Settings and conduct
Stem cells will be cultured in DMEM/F12 with 10% serum. The inflammatory niche will be provided with interleukin 1-beta. Ultracentrifugation purifies the extracellular vesicles of the cell culture supernatant. Centrifugation at 110,000g for 3hours allows the exosomes to precipitate. Exosomes are resolved in PBS and after the QC tests will be prescribed at 100 million/kg. The patient, treating physician, and the physician who follow-up are blinded.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
1- Definitive infection with COVID-19 confirmed by PCR
2- Acute respiratory distress Syndrome of moderate to severe type (PaO2/ FiO2 <200mmHg)
3- Age between 18 to 65 years from both Sexes
4- No Participation in another clinical trial during this study
5- Written informed consent
Exclusion Criteria:
1- Malignant diseases
2- Pregnancy
3- Symptoms or history of liver or kidney failure
4- History of lung surgery or Lung transplantation
5- Having an autoimmune disease or Metabolic disorders (such as diabetes)
6- Severe trauma occurred within 14 days before screening
7- Who are undergoing hemodialysis or peritoneal dialysis
Intervention groups
1- Intravenous injection of 2ml normal saline contains umbilical cord mesenchymal stem cell-derived Exosomes
2- Intravenous injection of 2ml normal saline
Main outcome variables
Adverse reaction (AE) and severe adverse reaction (SAE); Time to clinical improvement (TTIC)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20201202049568N3
Registration date:2021-03-05, 1399/12/15
Registration timing:registered_while_recruiting
Last update:2021-03-05, 1399/12/15
Update count:0
Registration date
2021-03-05, 1399/12/15
Registrant information
Name
Rashin Mohseni
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 6694 8444
Email address
rashin_mohseni@yahoo.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-03-05, 1399/12/15
Expected recruitment end date
2021-05-05, 1400/02/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of the Safety and Efficiency of human Umbilical Cord Derived Mesenchymal Stem Cell Exosomes in patients with ARDS of COVID-19; An interventional randomized double-blind controlled clinical trial: phase I and II
Public title
Exosome therapy in ARDS patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Acute respiratory distress Syndrome of moderate to severe type (PaO2/ FiO2 <200mmHg)
Age range between 18 to 65 years
Men and Women
No participation in another clinical trial during this study
Patients who have given themselves and their families a full explanation of the study process and have obtained informed written consent
Chest X-ray showed bilateral infiltration with pulmonary edema
Definitive infection with COVID-19 confirmed by PCR
Exclusion criteria:
Cancer or malignant diseases
Pregnant women or planning to become pregnant
Inflammatory diseases
Symptoms or history of liver or kidney failure
History of lung surgery or Lung transplantation
Having an autoimmune disease
Metabolic disorders (such as diabetes)
Infectious viral infection
Proven blood clotting disorders
Participate in other clinical trials simultaneously
Severe trauma occurred within 14 days before screening
They are undergoing hemodialysis or peritoneal dialysis
Bone marrow transplantation
Have a history of epilepsy, need continuous anticonvulsant therapy
Age
From 18 years old to 65 years old
Gender
Both
Phase
1-2
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Sample size
Target sample size:
72
Randomization (investigator's opinion)
Randomized
Randomization description
In this study, the Stratified Block Randomization method is used to randomize patients in the intervention and control groups. Because patients with different intensities are in the study, classification is based on the type of need or lack of need for respiratory support. Patients who need respiratory support in the form of mechanical ventilation are classified in group A and patients who need nasal cannula or do not need respiratory support are classified in group B. The blocks used are of sizes 2, 4, and 8, and based on the probable number of people participating in the study with any severity of the disease, blocks with the appropriate volume are used to generate random codes. In order to place patients in control and intervention groups, a random sequence table is created with the help of SAS 9.1 software. Each patient is assigned a completely random sequence number, and random numbers are placed in envelopes (exactly the same, completely closed, with no transparency to view the contents of the envelope). Patients choose one of the envelopes as they wish. Envelopes are kept by a researcher, who does not participate in the study and is not aware of the type of study until the data is collected. Only in case of severe complications, the researcher will be notified through the main project partner to open the relevant envelope.
Blinding (investigator's opinion)
Double blinded
Blinding description
In this study, the participant in the intervention, his / her clinical caregiver, trial researcher, and outcome assessor did not know that they were prescribing the intervention drug or placebo.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tehran University of Medical Sciences
Street address
Children's Medical Center Hospital, Dr. Gharib Ave, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733151
Approval date
2020-11-21, 1399/09/01
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1399.782
Health conditions studied
1
Description of health condition studied
Acute Respiratory Distress Syndrome due to COVID-19
ICD-10 code
U07.1
ICD-10 code description
Acute respiratory distress syndrome
Primary outcomes
1
Description
Adverse reaction (AE) and severe adverse reaction (SAE)
Timepoint
At the beginning of the intervention and on days 2, 3, 4, 7 and 14 after the intervention
Method of measurement
Physical examination of pulmonary function test
Secondary outcomes
1
Description
Murray lung injury score
Timepoint
Baseline and Days 1, 2, 3, 7, 14, 28, and 60 after intervention
Method of measurement
Clinical checklist. The minimum value is 0 and the maximum is 16. Higher scores mean a worse outcome.
2
Description
PaO2/FiO2
Timepoint
Baseline and Day 3, Day7, Day14, Day28, Day60
Method of measurement
Oxygen index: the ratio of alveolar oxygen partial pressure to fraction of inspired oxygen
3
Description
The number of days the survivor was out of ICU
Timepoint
60 Days
Method of measurement
The number of days the survivor was out of ICU
4
Description
Blood biochemistry (CRP)
Timepoint
Baseline, day 5, 10, 20
Method of measurement
C-reactive protein (CRP, mg/mL) concentration in the plasma will be measured.
Intervention groups
1
Description
Intervention group: Phase one: 12 patients with COVID-19 in two groups of 6 with ARDS (each group includes intervention groups of 3). Phase Two: 60 patients with COVID-19-ARDS in two groups of 30 controls and intervention. Classified A and B in both control and intervention groups - Exosome receiving group (intervention groups) • Injection material: Umbilical Cord Stem Cell-derived exosomes• Injection rate: 100 million exosomes per kilogram of body weight • Injection carrier: Saline • Injection site: Intravenous
Category
Treatment - Other
2
Description
Control group: Conventional treatments used in ARDS