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Use of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Caused by 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04456361
Recruitment Status : Active, not recruiting
First Posted : July 2, 2020
Last Update Posted : August 4, 2022
Sponsor:
Information provided by (Responsible Party):
Instituto de Medicina Regenerativa

Tracking Information
First Submitted Date  ICMJE June 23, 2020
First Posted Date  ICMJE July 2, 2020
Last Update Posted Date August 4, 2022
Actual Study Start Date  ICMJE April 16, 2020
Estimated Primary Completion Date October 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2020)
Oxygen saturation [ Time Frame: Baseline, and at days 2, 4 and 14 post-treatment ]
Number of patients with changes in percentage of resting Oxygen saturation (%O2)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2020)
  • Oxygen pressure in inspiration [ Time Frame: Baseline, and at days 2, 4 and 14 post-treatment ]
    Changes in mmHg of Arterial partial pressure of oxygen / Fraction of inspiration O2 (PaO2/FiO2) in all participants
  • ground-glass opacity [ Time Frame: Baseline, and at day 14 post-treatment ]
    Changes in percentage of participants with reduction in bilateral ground-glass opacities
  • Pneumonia infiltration [ Time Frame: Baseline, and at day 14 post-treatment ]
    Changes in percentage of participants with reduction of pneumonia bilateral infiltration
  • Lactate dehydrogenase [ Time Frame: Baseline, and at days 4 and 14 post-treatment ]
    Number of participants with a reduction in Lactate dehydrogenase (mg/dL)
  • C-reactive protein [ Time Frame: Baseline, and at days 4 and 14 post-treatment ]
    Number of participants with a reduction in C-reactive protein (mg/dL)
  • D-dimer [ Time Frame: Baseline, and at days 4 and 14 post-treatment ]
    Number of participants with a reduction in D-dimer (mg/dL)
  • Ferritine [ Time Frame: Baseline, and at days 4 and 14 post-treatment ]
    Number of participants with a reduction in Ferritine (mg/dL)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Caused by COVID-19
Official Title  ICMJE A Study of Mesenchymal Stem Cells as a Treatment in Patients With Acute Respiratory Distress Syndrome Caused by COVID-19
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • ARDS, Human
  • Covid-19
Intervention  ICMJE Biological: Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords
Mesenchymal Stem Cells as a single-dose therapy via IV infusion at a dose of 1 X 10 8 cells.
Other Name: UCMSC
Study Arms  ICMJE Experimental: COVID-19 patients
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: Biological: Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2020)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2022
Estimated Primary Completion Date October 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04456361
Other Study ID Numbers  ICMJE MSC-ARDS-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Instituto de Medicina Regenerativa
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Instituto de Medicina Regenerativa
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jesus Perez Instituto de Medicina Regenerativa
Study Chair: Juan Parcero Instituto de Medicina Regenerativa
PRS Account Instituto de Medicina Regenerativa
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP