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Safety and Efficacy of Intravenous Wharton's Jelly Derived Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Due to 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: NCT04390152
Recruitment Status : Not yet recruiting
First Posted : May 15, 2020
Last Update Posted : May 19, 2020
Sponsor:
Collaborator:
Clinical Somer
Information provided by (Responsible Party):
BioXcellerator

Brief Summary:

Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis.

Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation.

These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.


Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: Wharton's jelly derived Mesenchymal stem cells. Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) Phase 1 Phase 2

Detailed Description:

SARS-CoV-2, virus culprit of the COVID 19 that emerged in China, has become now a worldwide problem, with more than three million cases al around the world as reported by the World Health Organization. This situation has put health systems under extreme pressure, being overwhelmed be the amount of patients requiring attention.

Around 5% of patients will require ICU internation, due to severe lung inflammation giving rise to Acute Respiratory Distress Syndrome (ARDS) and a cytokine storm that ultimately affects other organs. In this group, mortality can be as high as 40%.

Mesenchymal stem cells (MSC) have shown great immunomodulatory effects, and are used in other inflammatory conditions as autoimmune diseases, being safe and preliminary effective in improving patients health status. They exert their effect via paracrine and autocrine pathways and have been shown to reduce IL-1, IL-6, Tumor necrosis factor alpha and increase IL-10 in COVID 19 patients. One of the greater advantages of the MSC is that they express no Major Histocompatibility Complex, reducing the risk of host immune reaction.

Given their immunomodulatory effects, research in this topic showing their safety and experimental efficacy are needed, as therapies for severe patients are lacking. Patients, researchers and data analysts will be blinded, and ARDS patients will be randomly allocated in standard therapy plus MSC arm or standard therapy alone to answer these questions.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Patient code will be stored in sealed, opaque envelops with their respective codification. These envelops will be stored in Clinica Somer's Research Unit and the only person with access permission will be the pharmaceutical chemist in charge. Treatment delivery (MSC or placebo) will also be in charge of the chemist, guaranteeing blinding of patient and healthcare professionals. Data analysis will be done by people blind to the treatment received by each patient.
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Mesenchymal stem cell
WJ MSC 50*10e6, two doses plus standard treatment with hydroxychloroquine + Lopinavir/Ritonavir or Azithromycin and ventilation support.
Drug: Wharton's jelly derived Mesenchymal stem cells.
IV Wharton's jelly derived Mesenchymal stem cells, two doses

Active Comparator: Control group
Hydroxychloroquine, lopinavir/ritonavir and ventilation support plus placebo
Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
Standard therapy as per hospital protocol, hydroxychloroquine 400mg + Lopinavir/Ritonavir 400/100 or azithromycin 500mg and Placebo




Primary Outcome Measures :
  1. Intergroup mortality difference with treatment [ Time Frame: 28 days. ]
    Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.


Secondary Outcome Measures :
  1. Number of patients with treatment related adverse events [ Time Frame: 6 months. ]
    Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.

  2. Difference in days of mechanical ventilation between groups [ Time Frame: From ICU admission to 180 days. ]
    Evaluation of the effect of WJ-MSC in the time of mechanical ventilation compared between the two groups, as prolonged mechanical ventilation days are associated with higher complication risks as pneumonia, tracheostomy and death.

  3. Median reduction of days of hospitalization [ Time Frame: From hospital admission to 180 days. ]
    Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.

  4. Median reduction of days of oxygen needs [ Time Frame: From hospital admission to 180 days. ]
    Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.

  5. Difference between "Sequential Organ Failure Assessment" score between groups [ Time Frame: Baseline to 7 days ]
    "Sequential Organ Failure Assessment" (SOFA) score is a tool used to determine the beginning and evolution of multiorgan failure, ranging from 0 to 24, being 24 the worst scenario. It has been proven useful as an outcome predictor of mortality and ICU stay. The result is the addition of the evaluation of each organ or system. Effect of WJ-MSC in the SOFA score will be compared between the two groups.

  6. Difference between median Murray score between groups [ Time Frame: Baseline and 7 days ]

    Murray score is a tool used to classify lung injury. 0 = no lung injury, 0.1-2.5, mild to moderate lund injury, >2.5 Acute respiratory distress syndrome.

    The effect of WJ-MSC in the Murray score will be compared between the two groups.


  7. Difference in APACHE II score between groups [ Time Frame: Baseline and 7 days ]

    APACHE II is a prognostic score based on 12 different items obtained in the first 24 hours of ICU admission. Its mainly used as a single measure, but some authors have used and described prediction usefulness with repeated measures. It ranges from 0 to 71 points. Higher scores are related to higher ICU mortality.

    The effect of WJ-MSC in the APACHE II score will compared between the two groups.


  8. Difference in lymphocyte count between groups [ Time Frame: baseline and 21 days or discharge ]

    Evaluation of the effect of WJ-MSC in lymphocyte count measured in absolute number/mm3.

    These laboratory measures have been associated with COVID 19 severity.


  9. Changes in C reactive protein concentration between groups [ Time Frame: baseline and 21 days or discharge ]

    Evaluation of the effect of WJ-MSC in C reactive protein concentration between the two groups, measured in mg/dl.

    Highest levels have been associated with COVID 19 severity and inflammation.


  10. Changes in D dimer concentration [ Time Frame: baseline and 21 days or discharge ]
    Evaluation of the effect of WJ-MSC in D dimer between the two groups, measured in micrograms Highest levels have been associated with COVID 19 severity and thromboembolic complications.

  11. Changes in ferritin concentration [ Time Frame: baseline and 21 days or discharge ]

    Evaluation of the effect of WJ-MSC in ferritin compared between the two groups, measured in nanograms/ml.

    These laboratory measures have been associated with COVID 19 infection and severity.


  12. Changes in lactate dehydrogenase concentration [ Time Frame: baseline and 21 days or discharge ]

    Evaluation of the effect of WJ-MSC in LDH compared between the two groups, measured in units/liter.

    These laboratory measures have been associated with COVID 19 infection and severity.


  13. Impact on interleukin 6 concentrations between groups. [ Time Frame: Baseline and 7 days ]
    Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation.The effect of WJ-MSC in IL-6 will be compared between the two groups. It will be measured in picograms/ml.

  14. Impact on interleukin 8 concentrations between groups. [ Time Frame: Baseline and 7 days ]
    Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 8 will be compared between the two groups. It will be measured in picograms/ml.

  15. Impact on interleukin 10 concentrations between groups. [ Time Frame: Baseline and 7 days ]
    Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 10 will be compared between the two groups. It will be measured in picograms/ml.

  16. Impact on tumor necrosis factor alpha concentrations between groups. [ Time Frame: Baseline to 7 days. ]
    Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in TNF alpha will be compared between the two groups. It will be measured in nanograms/ml.


Other Outcome Measures:
  1. Changes in 6 minute walk between groups [ Time Frame: 6 months ]

    Evaluation of the effect of WJ-MSC in pulmonary function measured with 6 minute walk.

    6 minute walk is a test that gives information about pulmonary, cardiovascular and musculoskeletal functions. It measures the distance walked in 6 minutes in meters.


  2. Changes in Pulmonary Computed Tomography Scan between groups [ Time Frame: 6 months ]
    Evaluation of the effect of WJ-MSC in pulmonary function with thoracic CT scan. CT scan gives information about lung parenchyma, showing acute and chronic changes related to the underlying condition. Radiologic findings will be compared mainly comparing percentage of patients with pulmonary fibrosis.

  3. Changes in Spirometry between groups [ Time Frame: 6 months ]

    Evaluation of the effect of WJ-MSC in pulmonary function measured with spirometry, compared between the two groups. Spirometry gives information about lung volume and mobilization of air.

    Main parameters to be measured in spirometry are Forced Vital Capacity, Forced Expiratory Volume in 1 second and relation between these two to define if there is obstruction or restriction of airflow.


  4. Changes in health related quality of life between groups [ Time Frame: 6 months ]

    Evaluation of the effect of WJ-MSC in health related quality of life assessed by 36 Item Short Survey (SF-36).

    SF 36 is a patient reported tool. Each question is rated from 0 to 100, being 100 the best score possible. The scores are then compared to a population defined median score.

    Differences in global and specific scoring will be measured between groups.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • SARS-CoV-2 positive Real Time - Polymerase Chain Reaction
  • Moderate to severe Acute respiratory distress syndrome according to Murray classification.
  • PaO2/FiO2 less than 200 mmHg.
  • Within 36 hours of orotracheal intubation.
  • Absence of response with previous standard therapy.
  • Willing to participate in the study expressed by patient or responsible caregiver.
  • Not being in other clinical trial.

Exclusion Criteria:

  • Current pregnancy.
  • Cardiac rhythm abnormalities with instability.
  • Acute congestive heart failure/cardiogenic shock.
  • Severe comorbidities affecting mortality as defined by research group.
  • Cancer history in the past 5 years.
  • HIV, syphilis, hepatitis B or C.
  • Concomitant use of immunosuppressive therapy with contraindication to MSC.
  • Fivefold elevation of liver enzymes (ALT, AST).
  • Chronic kidney disease with glomerular filtration rate below 30ml/min or dialytic needs.

Information from the National Library of Medicine

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): NCT04390152


Contacts
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Contact: Alfredo Hernandez-Ruiz, MSc +5745699999 ext 5386 ahernandez@clinicasomer.com
Contact: Santiago Saldarriaga-Gomez, MSc +5746041815 santiago.saldarriaga@bioxcellerator.com

Locations
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Colombia
Clinical Somer
Rionegro, Antioquia, Colombia
Contact: Alfredo Hernandez-Ruiz, MSc    +574442630      
Sponsors and Collaborators
BioXcellerator
Clinical Somer
Investigators
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Principal Investigator: Alfredo Hernandez-Ruiz, MSc Clinica Somer
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Responsible Party: BioXcellerator
ClinicalTrials.gov Identifier: NCT04390152    
Other Study ID Numbers: BIOXSOMCOV001
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual data won't be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioXcellerator:
coronavirus
stem cell research
mesenchymal stem cell
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Ritonavir
Lopinavir
Azithromycin
Hydroxychloroquine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents