Use of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Caused by COVID-19
Primary Purpose
ARDS, Human, Covid-19
Status
Active
Phase
Early Phase 1
Locations
Mexico
Study Type
Interventional
Intervention
Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords
Sponsored by
About this trial
This is an interventional treatment trial for ARDS, Human
Eligibility Criteria
Inclusion Criteria:
- Ability to understand and the willingness to provide informed consent or a legally authorized representative.
- Diagnosis of Acute Respiratory Distress Syndrome according to the Berlin Definition following the failing of prior standard therapy, and other available therapies.
Mild: 200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg with PEEP or CPAP ≥ 5 cm H2Oc Moderate: 100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O Severe: PaO2/FIO2 ≤ 100 mm Hg with PEEP ≥ 5 cm H2O
- Diagnostic test positive for SARS-CoV-2
- Age ≥ 18 years
- Any man with a partner of child-bearing potential agrees to use adequate contraception which will include two of the following: hormonal or barrier method of birth control, or abstinence prior to study entry, for the duration of study participation, and for 30 days following completion of therapy.
Exclusion Criteria:
- Current or anticipated use of other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to MSC infusion plus any patently atopic patients who have a history of having experienced an episode of allergic anaphylaxis.
- Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease).
- Known diagnosis of human immunodeficiency virus (HIV) infection.
Sites / Locations
- Instituto de Medicina Regenerativa
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
COVID-19 patients
Arm Description
Treatment consistsof Mesenchymal Stem Cells administered as a one-time, single-dose therapy via IV infusion at a dose of 1 X 10 8 cells.
Outcomes
Primary Outcome Measures
Oxygen saturation
Number of patients with changes in percentage of resting Oxygen saturation (%O2)
Secondary Outcome Measures
Oxygen pressure in inspiration
Changes in mmHg of Arterial partial pressure of oxygen / Fraction of inspiration O2 (PaO2/FiO2) in all participants
ground-glass opacity
Changes in percentage of participants with reduction in bilateral ground-glass opacities
Pneumonia infiltration
Changes in percentage of participants with reduction of pneumonia bilateral infiltration
Lactate dehydrogenase
Number of participants with a reduction in Lactate dehydrogenase (mg/dL)
C-reactive protein
Number of participants with a reduction in C-reactive protein (mg/dL)
D-dimer
Number of participants with a reduction in D-dimer (mg/dL)
Ferritine
Number of participants with a reduction in Ferritine (mg/dL)
Full Information
NCT ID
NCT04456361
First Posted
June 23, 2020
Last Updated
August 2, 2022
Sponsor
Instituto de Medicina Regenerativa
1. Study Identification
Unique Protocol Identification Number
NCT04456361
Brief Title
Use of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Caused by COVID-19
Official Title
A Study of Mesenchymal Stem Cells as a Treatment in Patients With Acute Respiratory Distress Syndrome Caused by COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 16, 2020 (Actual)
Primary Completion Date
October 15, 2022 (Anticipated)
Study Completion Date
December 15, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Medicina Regenerativa
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a pilot phase, open label, non-randomized study for the treatment of ARDS in patients infected with COVID-19. Subjects will be enrolled and treated with one dose of mesenchymal stem cells and follow-up will occur 90 days post-treatment.
Detailed Description
A Study of Mesenchymal Stem Cells as a treatment in Patients with Acute Respiratory Distress Syndrome caused by COVID-19 is a pilot phase, open label, non-randomized study, with a single study center.
The current pandemic caused by the novel virus SARS-CoV-2 has lead to a health care crisis affecting hospitals, hospital workers and health care structure globally. Many countries are dealing with a disrupted infrastructure in health care and imminent economic downfall to an extent that has not been seen in recent years. COVID-19 has lead to a large number of deaths in several countries, and Mexico has not been an exception. Availability of supplies, hospital space and equipment for mechanical ventilation are running critically low, and it has been a challenge for hospitals coping with severe clinical symptoms in COVID-19. This disease is characterized by pneumonia, fever, cough and occasional diarrhea, and the severity has been largely attributed to the high affinity of the virus to Angiotensin-Converting Enzyme 2 (ACE2) as the main receptor, and the Type II Transmembrane Serine Protease TMPRSS2 as the main host protease that mediates S protein activation on primary target cells in the lung and small intestine.
Many agencies and professional societies are working worldwide in developing treatment guidelines to care for patients with COVID-19, since the present treatments are supportive but not yet curative, therefore these guidelines are based on scientific evidence and expert opinion, the use of an array of drugs approved for other indications, as well as multiple investigational agents that are being studied. Lately, Remdesivir, a novel small-molecule adenine nucleotide analogue antiviral drug that has shown efficacy against Ebola virus in rhesus monkeys has shown improvement in patients with oxygen support. The focus of the research for a cure of COVID-19 has been centered on the individual's response in an immunological context, where an over activation of the immune response can cause a production of a large quantity of inflammatory molecules resulting in a cytokine storm with severe physiological consequences. The cytokine storm induces an increase in inflammatory proteins that results in edema, improper oxygen exchange, acute respiratory distress syndrome (ARDS), other organ damage and secondary infection. In recent studies, mesenchymal stem cells (MSCs) have proven to decrease the hyper inflammatory response in the lungs, leading to a steady recovery in patients with ARDS. The use of umbilical cord mesenchymal stem cells (UC-MSCs) may prove a potential effective measure for the treatment of the cytokine storm induced by COVID-19.
A step forward in a treatment strategy for the novel virus infection in humans would be critical for treating COVID-19 and especially ARDS-induced severe pneumonia, which is currently depleting resources around the world. Because efforts to control lung injury via pharmacological agents have been unsuccessful, mesenchymal stem cell (MSC)-based therapy is being investigated, based on the characteristics of MSCs to self-renew in a limitless manner and their multipotency.
Furthermore, MSC-based therapies have demonstrated in the past of having sufficient promising effects in experimental treatment of ARDS via inhibition of alveolar collapse, collagen accumulation, and cell apoptosis in lung tissue. Recent studies found that administrating allogeneic MSCs in patients with ARDS resulted in no pre-specified adverse events, including hypoxemia, cardiac arrhythmia, and ventricular tachycardia. MSCs are currently attracting interest due to source potential, a high proliferation rate, and a painless procedure that is free of ethical issues. Selection of a starting dose of approximately 100 million cells has been chosen to approximate the standard dosage of cells employed in prior clinical studies. This dosage may be adjusted depending on the data generated during the conduction of the study.
MSCs play a positive role mainly in two ways, namely immunomodulatory effects and differentiation abilities. MSCs can secrete many types of cytokines by paracrine secretion or make direct interactions with immune cells, leading to immunomodulation. The immunomodulatory effects of MSCs are triggered further by the activation of TLR receptor in MSCs, which is stimulated by pathogen-associated molecules such as LPS or double-stranded RNA from virus, like the HCoV-19.
There are many pilot studies conducted with MSC transplantation to explore their therapeutic potential for HCoV-19 infected patients, in many of them the pulmonary function and symptoms of patients were significantly improved days after MSC transplantation. Thus, in this study we intend to prove the intravenous transplantation of MSCs as safe and effective for treatment in patients with COVID-19 pneumonia, especially for patients in severe condition.
Primary Objective: To determine the feasibility and safety of intravenously administered MSCs in patients with Acute Respiratory Distress Syndrome.
Secondary Objectives:
To assess preliminary response in respiratory performance in patients with ARDS.
To assess overall survival of patients. To determine mortality rate at 14 days post treatment. To assess clinical and radiological improvements in patients.
Number of Subjects to be studied: 10
Endpoints
Primary Endpoint:
Evaluate Respiratory distress symptoms based on Berlin definition (RR; Oxygen saturation at rest; Arterial partial pressure of oxygen (PaO2) / Fraction of inspiration O2 (FiO2)).
Determine the degree of ground-glass opacity and pneumonia infiltration in imaging studies (X-ray or CT).
Evaluate clinical improvement based on APACHE II Score. Determine mortality rate at 2 weeks post treatment.
Secondary Endpoints:
Adverse events related to MSC infusion (description, timing, grade, seriousness, and relatedness) Hematological decompensation (based on CBC, SQ and metabolic panels) Objective response rate Progression free survival, overall survival, and best overall response rate Determine if any infusion reactions/toxicity occurs
Clinical and radiological parameters will be assessed at Baseline, 2, 4 and 14 day post-treatment, and there will be a 3 month follow-up by telephone contact.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, Human, Covid-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
COVID-19 patients
Arm Type
Experimental
Arm Description
Treatment consistsof Mesenchymal Stem Cells administered as a one-time, single-dose therapy via IV infusion at a dose of 1 X 10 8 cells.
Intervention Type
Biological
Intervention Name(s)
Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords
Other Intervention Name(s)
UCMSC
Intervention Description
Mesenchymal Stem Cells as a single-dose therapy via IV infusion at a dose of 1 X 10 8 cells.
Primary Outcome Measure Information:
Title
Oxygen saturation
Description
Number of patients with changes in percentage of resting Oxygen saturation (%O2)
Time Frame
Baseline, and at days 2, 4 and 14 post-treatment
Secondary Outcome Measure Information:
Title
Oxygen pressure in inspiration
Description
Changes in mmHg of Arterial partial pressure of oxygen / Fraction of inspiration O2 (PaO2/FiO2) in all participants
Time Frame
Baseline, and at days 2, 4 and 14 post-treatment
Title
ground-glass opacity
Description
Changes in percentage of participants with reduction in bilateral ground-glass opacities
Time Frame
Baseline, and at day 14 post-treatment
Title
Pneumonia infiltration
Description
Changes in percentage of participants with reduction of pneumonia bilateral infiltration
Time Frame
Baseline, and at day 14 post-treatment
Title
Lactate dehydrogenase
Description
Number of participants with a reduction in Lactate dehydrogenase (mg/dL)
Time Frame
Baseline, and at days 4 and 14 post-treatment
Title
C-reactive protein
Description
Number of participants with a reduction in C-reactive protein (mg/dL)
Time Frame
Baseline, and at days 4 and 14 post-treatment
Title
D-dimer
Description
Number of participants with a reduction in D-dimer (mg/dL)
Time Frame
Baseline, and at days 4 and 14 post-treatment
Title
Ferritine
Description
Number of participants with a reduction in Ferritine (mg/dL)
Time Frame
Baseline, and at days 4 and 14 post-treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to understand and the willingness to provide informed consent or a legally authorized representative.
Diagnosis of Acute Respiratory Distress Syndrome according to the Berlin Definition following the failing of prior standard therapy, and other available therapies.
Mild: 200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg with PEEP or CPAP ≥ 5 cm H2Oc Moderate: 100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O Severe: PaO2/FIO2 ≤ 100 mm Hg with PEEP ≥ 5 cm H2O
Diagnostic test positive for SARS-CoV-2
Age ≥ 18 years
Any man with a partner of child-bearing potential agrees to use adequate contraception which will include two of the following: hormonal or barrier method of birth control, or abstinence prior to study entry, for the duration of study participation, and for 30 days following completion of therapy.
Exclusion Criteria:
Current or anticipated use of other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to MSC infusion plus any patently atopic patients who have a history of having experienced an episode of allergic anaphylaxis.
Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease).
Known diagnosis of human immunodeficiency virus (HIV) infection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jesus Perez
Organizational Affiliation
Instituto de Medicina Regenerativa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juan Parcero
Organizational Affiliation
Instituto de Medicina Regenerativa
Official's Role
Study Chair
Facility Information:
Facility Name
Instituto de Medicina Regenerativa
City
Tijuana
State/Province
Baja California
ZIP/Postal Code
22100
Country
Mexico
12. IPD Sharing Statement
Learn more about this trial
Use of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Caused by COVID-19
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