Acute Respiratory Distress SyndromePhase 1/2NCT04390152
Safety and Efficacy of Intravenous Wharton's Jelly Derived Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Due to COVID 19
A Phase 1/2 study testing Wharton's jelly derived Mesenchymal stem cells. in people with Acute Respiratory Distress Syndrome, run by BioXcellerator at 2 sites in Colombia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Wharton's jelly derived Mesenchymal stem cells.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 2 sitesColombia
- Study dates
- 13 Jan 2020to 3 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Colombia2 sites
BioXcellerator
Medellín, Antioquia-CO, 050022
Clinical Somer
Rionegro, Antioquia
About this study
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
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.
Read the 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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Wharton's jelly derived Mesenchymal stem cells., Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
- Keywords
- coronavirus, stem cell research, mesenchymal stem cell
- Medical subject headings
- Respiratory Distress Syndrome, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Wharton's jelly derived Mesenchymal stem cells.Drug
IV Wharton's jelly derived Mesenchymal stem cells, two doses
Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)Drug
Standard therapy as per hospital protocol, hydroxychloroquine 400mg + Lopinavir/Ritonavir 400/100 or azithromycin 500mg and Placebo
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal stem cell | Experimental | WJ MSC 50*10e6, two doses plus standard treatment with hydroxychloroquine + Lopinavir/Ritonavir or Azithromycin and ventilation support. Receives: Drug: Wharton's jelly derived Mesenchymal stem cells. |
| Control group | Active comparator | Hydroxychloroquine, lopinavir/ritonavir and ventilation support plus placebo Receives: Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intergroup mortality difference with treatment
Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.
Measured: 28 days.
Secondary outcomes (16)
Number of patients with treatment related adverse events
Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.
Measured: 6 months.
Difference in days of mechanical ventilation between groups
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.
Measured: From ICU admission to 180 days.
Median reduction of days of hospitalization
Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.
Measured: From hospital admission to 180 days.
Median reduction of days of oxygen needs
Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.
Measured: From hospital admission to 180 days.
Difference between "Sequential Organ Failure Assessment" score between groups
"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.
Measured: Baseline to 7 days
Difference between median Murray score between groups
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.
Measured: Baseline and 7 days
Difference in APACHE II score between groups
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.
Measured: Baseline and 7 days
Difference in lymphocyte count between groups
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.
Measured: baseline and 21 days or discharge
Changes in C reactive protein concentration between groups
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.
Measured: baseline and 21 days or discharge
Changes in D dimer concentration
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.
Measured: baseline and 21 days or discharge
Changes in ferritin concentration
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.
Measured: baseline and 21 days or discharge
Changes in lactate dehydrogenase concentration
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.
Measured: baseline and 21 days or discharge
Impact on interleukin 6 concentrations between groups.
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.
Measured: Baseline and 7 days
Impact on interleukin 8 concentrations between groups.
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.
Measured: Baseline and 7 days
Impact on interleukin 10 concentrations between groups.
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.
Measured: Baseline and 7 days
Impact on tumor necrosis factor alpha concentrations between groups.
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.
Measured: Baseline to 7 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2020
- Study start13 Jan 2020
- Primary completion3 Mar 2022
- Study completion3 Mar 2022
Why it stopped: Stopped by the IP, because the first 6 patients recruited had died and it was unknown if it represented any safety risk or if the sample was insufficient to evaluate the study hypotesis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioXcellerator
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alfredo Hernandez-Ruiz, MSc, Principal investigator, Clinica Somer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04390152
- Sponsor's protocol ID
- BIOXSOMCOV001
- Status last verified
- Aug 2024
- First submitted
- 12 May 2020
- Last updated
- 27 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual data won't be shared.
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04390152
- Acronym / sponsor ID
- BIOXSOMCOV001
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- coronavirus, stem cell research, mesenchymal stem cell
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopped by the IP, because the first 6 patients recruited had died and it was unknown if it represented any safety risk or if the sample was insufficient to evaluate the study hypotesis.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- BioXcelleratorIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 3 Mar 2022 (actual)
- Study completion
- 3 Mar 2022 (actual)
- First posted
- 15 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal stem cell | Experimental | Drug: Wharton's jelly derived Mesenchymal stem cells.WJ MSC 50*10e6, two doses plus standard treatment with hydroxychloroquine + Lopinavir/Ritonavir or Azithromycin and ventilation support. |
| Control group | Active comparator | Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)Hydroxychloroquine, lopinavir/ritonavir and ventilation support plus placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Wharton's jelly derived Mesenchymal stem cells.IV Wharton's jelly derived Mesenchymal stem cells, two doses | Drug | Mesenchymal stem cell |
| 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 | Drug | Control group |
Primary outcome
Intergroup mortality difference with treatment
Time frame: 28 days.
Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.
16 secondary outcomes
Number of patients with treatment related adverse events
Time frame: 6 months.
Difference in days of mechanical ventilation between groups
Time frame: From ICU admission to 180 days.
Median reduction of days of hospitalization
Time frame: From hospital admission to 180 days.
Median reduction of days of oxygen needs
Time frame: From hospital admission to 180 days.
Difference between "Sequential Organ Failure Assessment" score between groups
Time frame: Baseline to 7 days
Difference between median Murray score between groups
Time frame: Baseline and 7 days
Difference in APACHE II score between groups
Time frame: Baseline and 7 days
Difference in lymphocyte count between groups
Time frame: baseline and 21 days or discharge
Changes in C reactive protein concentration between groups
Time frame: baseline and 21 days or discharge
Changes in D dimer concentration
Time frame: baseline and 21 days or discharge
Changes in ferritin concentration
Time frame: baseline and 21 days or discharge
Changes in lactate dehydrogenase concentration
Time frame: baseline and 21 days or discharge
Impact on interleukin 6 concentrations between groups.
Time frame: Baseline and 7 days
Impact on interleukin 8 concentrations between groups.
Time frame: Baseline and 7 days
Impact on interleukin 10 concentrations between groups.
Time frame: Baseline and 7 days
Impact on tumor necrosis factor alpha concentrations between groups.
Time frame: Baseline to 7 days.
Results and safety
The study was stopped early (reason given: Stopped by the IP, because the first 6 patients recruited had died and it was unknown if it represented any safety risk or if the sample was insufficient to evaluate the study hypotesis.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Individual participant dataSharing planned: No. Individual data won't be shared.
Related trials for Acute Respiratory Distress Syndrome
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Hernandez-Ruiz, MSc principal investigator
Clinica Somer
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Wharton's jelly derived Mesenchymal stem cells. in people with Acute Respiratory Distress Syndrome, run by BioXcellerator at 2 sites in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Stopped by the IP, because the first 6 patients recruited had died and it was unknown if it represented any safety risk or if the sample was insufficient to evaluate the study hypotesis.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intergroup mortality difference with treatment (time frame: 28 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2024.