Clinical trial NCT04933864: COVID-19 Treatment Using Methylene Blue and Photodynamic Therapy
Official title: The Clinical Trial of Methylene Blue Application Combined With Photodynamic Therapy for Treatment of SARS-CoV-2 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: SARS-CoV-2
Keywords: COVID-19
photodynamic therapy
methylene blue
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
Collaborators: name: Prokhorov General Physics Institute of the Russian Academy of Sciences (GPI RAS)
First posted: 2021-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
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
timeFrame: Day 2
Secondary outcomes:
measure: Comparison of oxygen saturation dynamics measured by pulse oximeter before and after treatment
timeFrame: 12 and 24 hours after photodynamic therapy
measure: The percentage of participants with positive dynamics in severity of pneumonia (e.g., from CT-4 to CT-2)
timeFrame: Day 14
measure: The percentage of participants having positive dynamics in patient status scale (EQ-5D-3L, SHOCS-COVID score) after treatment
timeFrame: Day 84
measure: The percentage of participants alive at day 28
timeFrame: Day 28
measure: The percentage of participants alive at day 84
timeFrame: Day 84
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University (Sechenov University)
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Igor V. Reshetov, Prof.
role: STUDY_DIRECTOR
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Artem A. Shiryaev, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Prokhorov General Physics Institute of the Russian Academy of Sciences
name: Victor B. Loschenov, Prof.
role: STUDY_CHAIR
References:
citation: 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