SARS-CoV-2Phase 1NCT04933864
COVID-19 Treatment Using Methylene Blue and Photodynamic Therapy
A Phase 1 study testing Methylene Blue and Photodynamic Therapy in people with SARS-CoV-2, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
Trial summary
According to the epidemiological situation worldwide and the number of vaccinations made, there is little success in the fight against COVID-19. For many reasons, methylene blue is a promising drug for an active treatment against SARS-CoV-2 infected patients. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- SARS-CoV-2
- What is being tested?
- Methylene Blue and Photodynamic Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteRussia
- Study dates
- 24 Apr 2020to 30 Jul 2020
- Phase
- Phase 1
- 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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- signed informed consent
- age: 18-90 years
- positive quantitative Polymerase Chain Reaction test on SARS-CoV-2 infection
- negative pregnancy test in women
- any severity of pneumonia (computer tomography scans)
- Non-inclusion Criteria:
Show all 13Show fewer
- documented refusal to participate in the study
- treatment with a serotonergic drug
- connection to artificial lung ventilation with or without sedation
- history of G-6-Phosphatase deficiency
- pregnancy and breastfeeding
- medical records of cirrhosis
- active chronic hepatitis
Who cannot join
- myocardial infarction, developed after the patient was included in the study, but before the intervention
- bleeding, developed after the patient was included in the study, but before the intervention
- connection to artificial lung ventilation developed after the patient was included in the study, but before the intervention
Trial locations and contacts
1 site in 1 country.
Russia1 site
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Moscow
About this study
Official title: The Clinical Trial of Methylene Blue Application Combined With Photodynamic Therapy for Treatment of SARS-CoV-2 Infected Patients
According to the epidemiological situation worldwide and the number of vaccinations made, there is little success in the fight against COVID-19. For many reasons, methylene blue is a promising drug for an active treatment against SARS-CoV-2 infected patients. Since methylene blue can work as a photosensitizer, photodynamic therapy as an antiviral treatment has great potential in the treatment of COVID-19. This clinical study investigated the effectiveness of SARS-CoV-2 infected people treatment using methylene blue and the following photodynamic therapy on the base of the L.L. Levshin Institute of Cluster Oncology (Department of Infectious Diseases №13) of I.M. Sechenov First Moscow State Medical University.
Read the detailed description
This is a randomized, parallel, single masking clinical study 60 participants aged 18-90 with one positive COVID-19 quantitative Polymerase Chain Reaction test and any severity of pneumonia (checked by computer tomography scans) were recruited. The experimental and control samples included 30 participants. Randomization was performed using the Random Number Table generated in STATISTICA Advanced 13.3. The physiological parameters including oxygen saturation, severity of pneumonia using computer tomography scans, heart rate, symptoms, and physical examination were collected. Participants in the experimental sample received methylthioninium chloride, Methylene Blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) orally in concentration 1 mg/kg in addition to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any. After 3 hours, photodynamic therapy of the participant's chest by a 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 18 J/cm^2 energy dose was performed for 50 minutes. If the participant is in a critical state, inhalation by 0.2 mg Methylene Blue 10 ml water solution and following photodynamic therapy of pharynx and nasal cavity using 650 nm laser source with 36 J/cm^2 energy dose during 10 minutes were performed. Participants in the control sample received only standard medical supportive therapy (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.). All next steps were performed for p participants from the experimental sample: 12 and 24 hours after photodynamic therapy, blood saturation were measured. 2 days after - participants will take a quantitative polymerase chain reaction test. 14 days after - computer tomography Aquilion One 640 (Canon Medical Systems Corporation, Registration Certificate FSZ 2008/01304, 02.07.2018) scans were performed. The participant's status scale (EQ-5D-3L, SHOCS-COVID score, validated) was checked on day 84. On 24 and 84 days all participants were checked whether they are alive or not by phone call. For participants in the control sample continuous check of blood saturation, quantitative Polymerase Chain Reaction tests after 2 and 14 days of treatment, and computer tomography scans were performed. The primary outcome of this study is to calculate the percentage of participants with negative quantitative Polymerase Chain Reaction test on SARS-CoV-2 by 2 days after methylene blue administration and photodynamic therapy. Experimental and control samples were comparable in gender, age, and severity of the disease. Z-test was used to analyze results on quantitative Polymerase Chain Reaction tests within control and experimental samples. For each sample paired Student t-test was used to analyze individual saturation changes. Wilcoxon criterion was used for data on severity of pneumonia and status scale.
- Conditions
- SARS-CoV-2
- Being tested
- Methylene Blue and Photodynamic Therapy
- Keywords
- COVID-19, photodynamic therapy, methylene blue
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene Blue and Photodynamic TherapyDrug
Also called Methylene Blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012), 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009)
Treatment group. Methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 1 mg/kg concentration orally one time were added to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any, and irradiation of the participant's chest was performed by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 18 J/cm^2 energy dose.
For critically ill participants: Inhalation by 0.2 mg methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 10 ml water solution and irradiation of pharynx and nasal cavity by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 36 J/cm^2 energy dose were performed.
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue and Photodynamic Therapy | Experimental | Methylene Blue 1 mg/kg water solution. Participants have orally received Methylene Blue solution of 1 mg/kg concentration one time in addition to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any. After 3 hours of Methylene Blue administration irradiation of chest using 650 nm laser source with 18 J/cm^2 energy dose was performed. Receives: Drug: Methylene Blue and Photodynamic Therapy |
| Control group | No intervention | COVID-19 positive participants treated with standard medical supportive therapy (e.g. azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.). |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of participants with negative quantitative Polymerase Chain Reaction test on SARS-CoV-2 on day 2 after methylene blue administration and photodynamic therapy
The percentage of participants with negative quantitative Polymerase Chain Reaction test was reported. Quantitative Polymerase Chain Reaction test was performed not earlier than 3-4 hours after the last meal, excluding the use of medicines for topical application (drops, sprays, etc.) before taking the test.
Measured: Day 2
Secondary outcomes (5)
Comparison of oxygen saturation dynamics measured by pulse oximeter before and after treatment
The saturation dynamics after photodynamic therapy in 12 and 24 hours were reported
Measured: 12 and 24 hours after photodynamic therapy
The percentage of participants with positive dynamics in severity of pneumonia (e.g., from CT-4 to CT-2)
The percentage of participants that have a positive trend in severity of pneumonia (computer tomography scans) after treatment (e.g., from CT-4 to CT-2) was reported
Measured: Day 14
The percentage of participants having positive dynamics in patient status scale (EQ-5D-3L, SHOCS-COVID score) after treatment
The percentage of participants that have positive dynamics in patient status scale (EQ-5D-3L, SHOCS-COVID score) was calculated
Measured: Day 84
The percentage of participants alive at day 28
The percentage of participants still alive at day 28 of samples collection was reported
Measured: Day 28
The percentage of participants alive at day 84
The percentage of participants still alive at day 84 of samples collection was reported
Measured: Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study start24 Apr 2020
- Primary completion20 May 2020
- Study completion30 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV-2Studies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Prokhorov General Physics Institute of the Russian Academy of Sciences (GPI RAS)
- Responsible party
- Sponsor
- Investigators
- Igor V. Reshetov, Prof., Study director, I.M. Sechenov First Moscow State Medical University (Sechenov University)Artem A. Shiryaev, Ph.D., Principal investigator, I.M. Sechenov First Moscow State Medical University (Sechenov University)Victor B. Loschenov, Prof., Study chair, Prokhorov General Physics Institute of the Russian Academy of Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04933864
- Sponsor's protocol ID
- 2206
- Status last verified
- Jun 2021
- First submitted
- 15 Jun 2021
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The Local Ethics Committee of I.M. Sechenov First Moscow State Medical University did not give permission to provide individual participant data.
Publications
Strakhovskaya, M. G., Meerovich, G. A., Kuskov, A. N., Gonchukov, S. A., & Loschenov, V. B. (2020, September 1). Photoinactivation of coronaviruses: Going along the optical spectrum. Laser Physics Letters. IOP Publishing Ltd. https://doi.org/10.1088/1612-202X/abab14
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Trial of Methylene Blue Application Combined With Photodynamic Therapy for Treatment of SARS-CoV-2 Infected Patients
- ClinicalTrials.gov ID
- NCT04933864
- Acronym / sponsor ID
- 2206
- Conditions
- SARS-CoV-2
- Keywords
- COVID-19, photodynamic therapy, methylene blue
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Collaborators
- Prokhorov General Physics Institute of the Russian Academy of Sciences (GPI RAS)
- Study start
- 24 Apr 2020 (actual)
- Primary completion
- 20 May 2020 (actual)
- Study completion
- 30 Jul 2020 (actual)
- First posted
- 22 Jun 2021 (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.
According to the epidemiological situation worldwide and the number of vaccinations made, there is little success in the fight against COVID-19. For many reasons, methylene blue is a promising drug for an active treatment against SARS-CoV-2 infected patients. Since methylene blue can work as a photosensitizer, photodynamic therapy as an antiviral treatment has great potential in the treatment of COVID-19. This clinical study investigated the effectiveness of SARS-CoV-2 infected people treatment using methylene blue and the following photodynamic therapy on the base of the L.L. Levshin Institute of Cluster Oncology (Department of Infectious Diseases №13) of I.M. Sechenov First Moscow State Medical University.
Detailed description
This is a randomized, parallel, single masking clinical study 60 participants aged 18-90 with one positive COVID-19 quantitative Polymerase Chain Reaction test and any severity of pneumonia (checked by computer tomography scans) were recruited. The experimental and control samples included 30 participants. Randomization was performed using the Random Number Table generated in STATISTICA Advanced 13.3. The physiological parameters including oxygen saturation, severity of pneumonia using computer tomography scans, heart rate, symptoms, and physical examination were collected. Participants in the experimental sample received methylthioninium chloride, Methylene Blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) orally in concentration 1 mg/kg in addition to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any. After 3 hours, photodynamic therapy of the participant's chest by a 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 18 J/cm^2 energy dose was performed for 50 minutes. If the participant is in a critical state, inhalation by 0.2 mg Methylene Blue 10 ml water solution and following photodynamic therapy of pharynx and nasal cavity using 650 nm laser source with 36 J/cm^2 energy dose during 10 minutes were performed. Participants in the control sample received only standard medical supportive therapy (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.). All next steps were performed for p participants from the experimental sample: 12 and 24 hours after photodynamic therapy, blood saturation were measured. 2 days after - participants will take a quantitative polymerase chain reaction test. 14 days after - computer tomography Aquilion One 640 (Canon Medical Systems Corporation, Registration Certificate FSZ 2008/01304, 02.07.2018) scans were performed. The participant's status scale (EQ-5D-3L, SHOCS-COVID score, validated) was checked on day 84. On 24 and 84 days all participants were checked whether they are alive or not by phone call. For participants in the control sample continuous check of blood saturation, quantitative Polymerase Chain Reaction tests after 2 and 14 days of treatment, and computer tomography scans were performed. The primary outcome of this study is to calculate the percentage of participants with negative quantitative Polymerase Chain Reaction test on SARS-CoV-2 by 2 days after methylene blue administration and photodynamic therapy. Experimental and control samples were comparable in gender, age, and severity of the disease. Z-test was used to analyze results on quantitative Polymerase Chain Reaction tests within control and experimental samples. For each sample paired Student t-test was used to analyze individual saturation changes. Wilcoxon criterion was used for data on severity of pneumonia and status scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene Blue and Photodynamic Therapy | Experimental | Drug: Methylene Blue and Photodynamic TherapyMethylene Blue 1 mg/kg water solution. Participants have orally received Methylene Blue solution of 1 mg/kg concentration one time in addition to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any. After 3 hours of Methylene Blue administration irradiation of chest using 650 nm laser source with 18 J/cm^2 energy dose was performed. |
| Control group | No intervention | –COVID-19 positive participants treated with standard medical supportive therapy (e.g. azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- signed informed consent
- age: 18-90 years
- positive quantitative Polymerase Chain Reaction test on SARS-CoV-2 infection
- negative pregnancy test in women
- any severity of pneumonia (computer tomography scans)
Key exclusion criteria (3 listed)
- myocardial infarction, developed after the patient was included in the study, but before the intervention
- bleeding, developed after the patient was included in the study, but before the intervention
- connection to artificial lung ventilation developed after the patient was included in the study, but before the intervention
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 |
|---|---|---|
| Methylene Blue and Photodynamic TherapyAlso: Methylene Blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012), 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009)Treatment group. Methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 1 mg/kg concentration orally one time were added to the current therapy of the participant (e.g., azithromycin, hydroxychloroquine, aminodihydrophthalazinedione sodium, levofloxacin, etc.), if any, and irradiation of the participant's chest was performed by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 18 J/cm^2 energy dose. For critically ill participants: Inhalation by 0.2 mg methylene blue (SamaraMedProm, Russia, Registration number: MP-001834, 13.09.2012) 10 ml water solution and irradiation of pharynx and nasal cavity by 650 nm laser source (UFPh-675-01-BIOSPEC, BIOSPEC, Russia, Registration number: 2009/04648, 26.03.2009) with 36 J/cm^2 energy dose were performed. | Drug | Methylene Blue and Photodynamic Therapy |
Primary outcome
The percentage of participants with negative quantitative Polymerase Chain Reaction test on SARS-CoV-2 on day 2 after methylene blue administration and photodynamic therapy
Time frame: Day 2
The percentage of participants with negative quantitative Polymerase Chain Reaction test was reported. Quantitative Polymerase Chain Reaction test was performed not earlier than 3-4 hours after the last meal, excluding the use of medicines for topical application (drops, sprays, etc.) before taking the test.
5 secondary outcomes
Comparison of oxygen saturation dynamics measured by pulse oximeter before and after treatment
Time frame: 12 and 24 hours after photodynamic therapy
The percentage of participants with positive dynamics in severity of pneumonia (e.g., from CT-4 to CT-2)
Time frame: Day 14
The percentage of participants having positive dynamics in patient status scale (EQ-5D-3L, SHOCS-COVID score) after treatment
Time frame: Day 84
The percentage of participants alive at day 28
Time frame: Day 28
The percentage of participants alive at day 84
Time frame: Day 84
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- BackgroundStrakhovskaya, M. G., Meerovich, G. A., Kuskov, A. N., Gonchukov, S. A., & Loschenov, V. B. (2020, September 1). Photoinactivation of coronaviruses: Going along the optical spectrum. Laser Physics Letters. IOP Publishing Ltd. https://doi.org/10.1088/1612-202X/abab14
- Individual participant dataSharing planned: No. The Local Ethics Committee of I.M. Sechenov First Moscow State Medical University did not give permission to provide individual participant data.
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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.
Igor V. Reshetov, Prof. study director
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Artem A. Shiryaev, Ph.D. principal investigator
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Victor B. Loschenov, Prof. study chair
Prokhorov General Physics Institute of the Russian Academy of Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methylene Blue and Photodynamic Therapy in people with SARS-CoV-2, run by I.M. Sechenov First Moscow State Medical University 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 13 inclusion and 3 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: finished, as of the sponsor's last update on 22 Jun 2021. 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. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The percentage of participants with negative quantitative Polymerase Chain Reaction test on SARS-CoV-2 on day 2 after methylene blue administration and photodynamic therapy (time frame: Day 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04933864, which also lists 1 linked publication.
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 22 Jun 2021.