Covid19Phase 2COVID-19EXO2NCT04602442
Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Pneumonia
A Phase 2 study testing EXO 1 inhalation and EXO 2 inhalation in people with Covid19 and SARS-CoV-2 PNEUMONIA, run by Olga Tyumina at 1 site in Russia.
Trial summary
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- What is being tested?
- EXO 1 inhalation and EXO 2 inhalation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteRussia
- Study dates
- 1 Oct 2020to 30 Dec 2021
- Phase
- Phase 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the study objectives and risks and provide signed and dated informed consent;
- COVID-19 infection (by PCR or antibody test or high probability of COVID-19 by CT);
- Pneumonia requiring hospitalization, and oxygen saturation of <93%, need for noninvasive ventilation. The confirmed volume of lung damage by CT;
- ability to proceed with inhalation by self;
Who cannot join
- Severe respiratory failure at the time of screening due to COVID-19 pneumonia;
- Known to undergo medical resuscitation for 14 days before randomization;
- Any serious medical condition or deviation of the clinical laboratory parameter that, in the opinion of the researcher, prevents safe participation and completion of the study by the participant Confirmed uncontrolled active bacterial, fungal, viral or other infection (other than SARS-CoV-2).
- According to the researcher, the progression to death is inevitable and will occur within the next 24 hours, regardless of the therapy.
- The life expectancy of fewer than 28 days, taking into account a medical condition already existing that cannot be corrected, e.g. participants with the following conditions or suspicions: polyorganic insufficiency, poorly controlled neoplasms, terminal stage heart disease, cardiopulmonary cardiac arrest that required cardiopulmonary resuscitation, or electrical activity not accompanied by a pulse, or asystole within the last 30 days, terminal stage liver disease, terminal stage liver disease, or liver disease;
- Pregnancy or breastfeeding;
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- Liver function failure (Class C for Child-Pugh), detected within 24 hours at screening (local laboratory);
- Absolute neutrophil count (ANC) <500 cells/µL at screening (local laboratory);
- Platelet count <50000 cells/µL at screening (based on laboratory data);
- Creatinine level ≥ 1.5 from the upper limit;
- Uncontrolled or untreated arrhythmia with clinical manifestations, myocardial infarction within the last 6 weeks or congestive heart failure (NYHA Degrees 3 or 4);
- Respiratory failure in the last 6 months or home use of oxygen in severe chronic respiratory disease (COPD);
- Quadriplegia;
- Primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy, aspergillosis or other invasive mold/fungal infection in anamnesis, or internal or bone marrow transplantation for 6 months before randomization;
- Known infection with hepatitis B or C viruses requiring therapy;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Extended Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Two-Sided Pneumonia
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection.
According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes.
This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.
Read the detailed description
COVID-19 is an infectious disease caused by the most recently discovered coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries worldwide. Globally, as of 1:09 pm CEST, 27 July 2020, there have been 16 096 741 confirmed cases of COVID-19, including 646 384 deaths, reported to WHO.
The main and rapidly achievable target of SARS-CoV-2 is lung type II alveolar cells (AT2), which determines the development of diffuse alveolar damage. In the pathogenesis of ARDS due to COVID-19, the main role is played by an over-response of the immune system with rapidly developing severe life-threatening cytokine release syndrome (cytokine storm). Cytokine release syndrome threatens the emergence and progression of ARDS. The key components of the pathogenesis of ARDS also include disruption of cell cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes and macrophages with a massive release of proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor, monocytic chemoattractive protein 1), and inflammatory markers (CRP, serum ferritin), infiltration of internal organs and tissues by activated T-lymphocytes and macrophages, resulting in a hyperinflammatory reaction. Such severe lesions can lead to death or severe lung damage, including long rehabilitation after discharge.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) may significantly reduce lung inflammation and pathological impairment resulting from different types of lung injury. Many researchers connect the anti-inflammatory effect of MSC with their secretome which includes MSC derived exosomes. It is highly likely that MSC exosomes have the same therapeutic effect on inoculation pneumonia as MSCs themselves. Moreover, exosomes show a strong effect of regenerative stimulation on different wounds so the regenerative effect can be extended on patients with COVID-19 pneumonia.
The purpose of this protocol is to explore the safety and efficiency of aerosol inhalation of the exosomes in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
- Conditions
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- Being tested
- EXO 1 inhalation, EXO 2 inhalation, Placebo inhalation
- Keywords
- Covid-19, SARS-CoV-2, exosomes, MSC
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXO 1 inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the first type.
EXO 2 inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the second type.
Placebo inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes).
| Study group | Role | What they receive |
|---|---|---|
| EXO-1 | Experimental | Participants (n=30) in this group will receive standard therapy and exosomes of the first type. Receives: Drug: EXO 1 inhalation |
| EXO-2 | Experimental | Participants (n=30) in this group will receive standard therapy and exosomes of the second type. Receives: Drug: EXO 2 inhalation |
| Placebo | Placebo comparator | Participants (n=30) in this group will receive standard therapy and inhalation placebo solution. Receives: Drug: Placebo inhalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with non-serious and serious adverse events during trial
Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial
Measured: through study, an average of 2 months
Number of participants with non-serious and serious adverse during inhalation procedure
Safety assessments such as adverse events during the inhalation procedures will be registered.
Measured: 10 days during inhalation procedures
Secondary outcomes (8)
Time to clinical recovery (TTCR)
Measure and compare time to clinical recovery and clinical discharge compare to placebo.
Measured: up to 2 months
SpO2 concentration changes
Concentration of SpO2 by Pulse oximetry device during procedures and compare to placebo.
Measured: up to 2 months
Chest Imaging Changes
Chest imaging changes for 30 days compared to placebo. Information on the percent of damaged lungs will be analyzed and reported.
Measured: Three times. At diagnosis, 10-14 days after treatment and 30 days after clinic discharge
Blood biochemistry (CRP)
C-reactive protein (CRP, mg/L) concentration in the plasma will be measured. The result will be analyzed and compared in time.
Measured: Baseline, day 5, 10, 20
Procalcitonin concentration
Procalcitonin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.
Measured: Baseline, day 5, 10, 20
Ferritin concentration
Ferritin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.
Measured: Baseline, day 5, 10, 20
Creatinine concentration
Creatinine concentration (umol/L) in plasma will be measured. The result will be analyzed and compared in time.
Measured: Baseline, day 5, 10, 20
Urea concentration
Urea concentration (mmol/L) in plasma will be measured. The result will be analyzed and compared in time.
Measured: Baseline, day 5, 10, 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study start1 Oct 2020
- Primary completion1 Aug 2021 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The trial has three groups, each with 30 subjects (n=90). All eligible study subjects will be randomized, double-blinded, to either the two treatment groups or placebo group.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Olga Tyumina
- Sponsor type
- University, hospital or other
- Collaborators
- Samara State Medical University, Samara Regional Clinical Hospital V.D. Seredavin
- Responsible party
- Sponsor-investigator, Olga Tyumina, State-Financed Health Facility "Samara Regional Medical Center Dinasty"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04602442
- Sponsor's protocol ID
- COVID-19 EXO Extended
- Acronym
- COVID-19EXO2
- Status last verified
- Oct 2020
- First submitted
- 21 Oct 2020
- Last updated
- 26 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Extended Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Two-Sided Pneumonia
- ClinicalTrials.gov ID
- NCT04602442
- Acronym / sponsor ID
- COVID-19EXO2 / COVID-19 EXO Extended
- Conditions
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- Keywords
- Covid-19, SARS-CoV-2, exosomes, MSC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Olga TyuminaUniversity, hospital or other
- Collaborators
- Samara State Medical University, Samara Regional Clinical Hospital V.D. Seredavin
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Aug 2021 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 26 Oct 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.
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection.
According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes.
This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.
Detailed description
COVID-19 is an infectious disease caused by the most recently discovered coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries worldwide. Globally, as of 1:09 pm CEST, 27 July 2020, there have been 16 096 741 confirmed cases of COVID-19, including 646 384 deaths, reported to WHO.
The main and rapidly achievable target of SARS-CoV-2 is lung type II alveolar cells (AT2), which determines the development of diffuse alveolar damage. In the pathogenesis of ARDS due to COVID-19, the main role is played by an over-response of the immune system with rapidly developing severe life-threatening cytokine release syndrome (cytokine storm). Cytokine release syndrome threatens the emergence and progression of ARDS. The key components of the pathogenesis of ARDS also include disruption of cell cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes and macrophages with a massive release of proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor, monocytic chemoattractive protein 1), and inflammatory markers (CRP, serum ferritin), infiltration of internal organs and tissues by activated T-lymphocytes and macrophages, resulting in a hyperinflammatory reaction. Such severe lesions can lead to death or severe lung damage, including long rehabilitation after discharge.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) may significantly reduce lung inflammation and pathological impairment resulting from different types of lung injury. Many researchers connect the anti-inflammatory effect of MSC with their secretome which includes MSC derived exosomes. It is highly likely that MSC exosomes have the same therapeutic effect on inoculation pneumonia as MSCs themselves. Moreover, exosomes show a strong effect of regenerative stimulation on different wounds so the regenerative effect can be extended on patients with COVID-19 pneumonia.
The purpose of this protocol is to explore the safety and efficiency of aerosol inhalation of the exosomes in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
- Model description
- The trial has three groups, each with 30 subjects (n=90). All eligible study subjects will be randomized, double-blinded, to either the two treatment groups or placebo group.
| Arm | Type | Receives |
|---|---|---|
| EXO-1 | Experimental | Drug: EXO 1 inhalationParticipants (n=30) in this group will receive standard therapy and exosomes of the first type. |
| EXO-2 | Experimental | Drug: EXO 2 inhalationParticipants (n=30) in this group will receive standard therapy and exosomes of the second type. |
| Placebo | Placebo comparator | Drug: Placebo inhalationParticipants (n=30) in this group will receive standard therapy and inhalation placebo solution. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Ability to understand the study objectives and risks and provide signed and dated informed consent;
- COVID-19 infection (by PCR or antibody test or high probability of COVID-19 by CT);
- Pneumonia requiring hospitalization, and oxygen saturation of <93%, need for noninvasive ventilation. The confirmed volume of lung damage by CT;
- ability to proceed with inhalation by self;
Key exclusion criteria (15 listed)
- Severe respiratory failure at the time of screening due to COVID-19 pneumonia;
- Known to undergo medical resuscitation for 14 days before randomization;
- Any serious medical condition or deviation of the clinical laboratory parameter that, in the opinion of the researcher, prevents safe participation and completion of the study by the participant Confirmed uncontrolled active bacterial, fungal, viral or other infection (other than SARS-CoV-2).
- According to the researcher, the progression to death is inevitable and will occur within the next 24 hours, regardless of the therapy.
- The life expectancy of fewer than 28 days, taking into account a medical condition already existing that cannot be corrected, e.g. participants with the following conditions or suspicions: polyorganic insufficiency, poorly controlled neoplasms, terminal stage heart disease, cardiopulmonary cardiac arrest that required cardiopulmonary resuscitation, or electrical activity not accompanied by a pulse, or asystole within the last 30 days, terminal stage liver disease, terminal stage liver disease, or liver disease;
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 |
|---|---|---|
| EXO 1 inhalationTwice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the first type. | Drug | EXO-1 |
| EXO 2 inhalationTwice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the second type. | Drug | EXO-2 |
| Placebo inhalationTwice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes). | Drug | Placebo |
Primary outcome
Number of participants with non-serious and serious adverse events during trial
Time frame: through study, an average of 2 months
Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial
Number of participants with non-serious and serious adverse during inhalation procedure
Time frame: 10 days during inhalation procedures
Safety assessments such as adverse events during the inhalation procedures will be registered.
8 secondary outcomes
Time to clinical recovery (TTCR)
Time frame: up to 2 months
SpO2 concentration changes
Time frame: up to 2 months
Chest Imaging Changes
Time frame: Three times. At diagnosis, 10-14 days after treatment and 30 days after clinic discharge
Blood biochemistry (CRP)
Time frame: Baseline, day 5, 10, 20
Procalcitonin concentration
Time frame: Baseline, day 5, 10, 20
Ferritin concentration
Time frame: Baseline, day 5, 10, 20
Creatinine concentration
Time frame: Baseline, day 5, 10, 20
Urea concentration
Time frame: Baseline, day 5, 10, 20
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2020.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EXO 1 inhalation and EXO 2 inhalation in people with Covid19 and SARS-CoV-2 PNEUMONIA, run by Olga Tyumina at 1 site in Russia.
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 4 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 26 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
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?
Number of participants with non-serious and serious adverse events during trial (time frame: through study, an average of 2 months). The study lists 2 primary outcomes in all. 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 26 Oct 2020.