Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19

Sponsor

Promomed, LLC (Other)

Overall Status

Completed

CT.gov ID

NCT05939622

Collaborator

(none)

Enrollment

Location

Arms

7.1

Actual Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Asthenia COVID-19 Functional MRI Cognitive Impairment	Other: Structural and functional MRI Drug: Ethyl methyl hydroxypyridine succinate + Meldonium Drug: Placebo	Phase 4

Detailed Description

A prospective, randomized, double-blind, placebo-controlled trial to evaluate the effectiveness of therapy using functional MRI of the brain in the setting of neuroprotective therapy for the treatment of patients with chronic fatigue syndrome after COVID-19. The study included 30 patients matched by sex and age with confirmed coronavirus infection. All patients were examined with MFI-20, MoCa, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy with EMHPS-M or placebo (15 patients each) using resting state fMRI and with cognitive paradigm. First group received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate

500 mg of meldonium) once per day for 10 days. Second group received Placebo in the same way.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Prospective Randomized Double Blind Placebo Controlled Study of Efficacy of the Therapy With BRAINMAX® Using Functional Magnetic Resonance Imaging (fMRI) for the Treatment of Patients With Post-COVID Asthenic Syndrome

Actual Study Start Date :

May 18, 2022

Actual Primary Completion Date :

Dec 20, 2022

Actual Study Completion Date :

Dec 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: fMRI with subsequent injection of active drug (Ethyl methyl hydroxypyridine succinate + Meldonium) Arm 1 (n=15) performed structural and functional MRI and received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) once per day for 10 days	Other: Structural and functional MRI MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy, using resting state fMRI and with cognitive paradigm. Other Names: fMRI Drug: Ethyl methyl hydroxypyridine succinate + Meldonium Ethyl methyl hydroxypyridine succinate 100.0 mg/mL, meldonium dihydrate - 100.0 mg/mL (Solution for intravenous and intramuscular administration) Other Names: BRAINMAX®
Placebo Comparator: fMRI with subsequent injection of placebo Arm 2 (n=15) performed structural and functional MRI and received Placebo in the same way.	Other: Structural and functional MRI MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy, using resting state fMRI and with cognitive paradigm. Other Names: fMRI Drug: Placebo Placebo was used in the same way

Arm

Intervention/Treatment

Experimental: fMRI with subsequent injection of active drug (Ethyl methyl hydroxypyridine succinate + Meldonium)

Arm 1 (n=15) performed structural and functional MRI and received intramuscularly with the dosage regimen of 5 mL of solution (500 mg of ethyl methyl hydroxypyridine succinate + 500 mg of meldonium) once per day for 10 days

Other: Structural and functional MRI

MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy, using resting state fMRI and with cognitive paradigm.

Other Names:

fMRI

Drug: Ethyl methyl hydroxypyridine succinate + Meldonium

Ethyl methyl hydroxypyridine succinate 100.0 mg/mL, meldonium dihydrate - 100.0 mg/mL (Solution for intravenous and intramuscular administration)

Other Names:

BRAINMAX®

Placebo Comparator: fMRI with subsequent injection of placebo

Arm 2 (n=15) performed structural and functional MRI and received Placebo in the same way.

Other: Structural and functional MRI

MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy, using resting state fMRI and with cognitive paradigm.

Other Names:

fMRI

Drug: Placebo

Placebo was used in the same way

Outcome Measures

Primary Outcome Measures

Changing patterns of brain activation using task fMRI with a cognitive paradigm [From baseline to Visit 2 (day 10)]
Changing patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking Brainmax in comparison with placebo in patients with post-COVID asthenic syndrome.

Secondary Outcome Measures

Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the parenteral therapy [From baseline to Visit 2 (day 10)]
MFI-20 has an even proportion of positively and negatively worded items that are rated on a 5-point Likert scale. Subscale scores (range 4-20) are calculated as the sum of item ratings and a total fatigue score (range 20-100) is calculated as the sum of subscale scores. Higher scores indicate a higher level of fatigue. Mean decrease of MFI-20 asthenia scale score after the completion of the parenteral therapy
Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the parenteral therapy [From baseline to Visit 2 (day 10)]
The FAS is a 10-item general fatigue questionnaire to assess fatigue. Five questions reflect physical fatigue and 5 questions (questions 3 and 6-9) mental fatigue. Subsequently, the total FAS score can be calculated by summing the scores on all questions (recoded scores for questions 4 and 10). The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue. Score dynamics by FAS-10 scale after the completion of the parenteral therapy
Cognitive function on a Montreal Cognitive Assessment (MoCA) scale after the completion of the parenteral therapy [From baseline to Visit 2 (day 10)]
The Montreal Cognitive Assessment (MoCA) is a test used by healthcare providers to evaluate people with memory loss or other symptoms of cognitive decline. Scores on the MoCA range from zero to 30. A score of 26 and higher is considered normal. Score dynamics by MoCA scale after the completion of the parenteral therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients able to sign the patient informed consent form for the participation in the clinical study
Patients of both sexes of 25-50 years of age
Patient's negative test result for severe acute respiratory syndrome (SARS) -CoV-2 RNA obtained by polymerase chain reaction (PCR) method within 72 hours
COVID-19 diagnosis documented in the history more than 12 weeks ago*
Symptoms of Post-COVID-19 syndrome (asthenic state, feeling of energy loss and decreased functioning, intellectual function disorder, attention and memory disorder, emotional lability, reducing stress resistance) which appeared during or after COVID-19, retain for more than 12 weeks and cannot be explained by an alternative diagnosis
Patients capable of following the requirements of the Clinical Study Protocol
Negative pregnancy test result (for women with the active childbearing potential)
MFI-20 scale score is more than 30 at the moment of screening.
Higher education.
Lack of decompensated somatic pathology
Lack of indications of the transferred/current disease of the nervous system

Exclusion Criteria:

Allergic reactions to the components of the study product
Taking prohibited drugs/dietary supplements during the previous randomization of the month
Severe hepatic failure
Severe renal failure
Chronic liver and hepatic diseases
Thyroid diseases
Anaemia
Malignant tumour of any localization currently or during 5 years before the inclusion into the study except for completely treated carcinoma in situ
Autoimmune diseases
Other chronical diseases which, according to the investigator, can cause asthenia
Pregnancy or lactation period
Tuberculosis, cancers or positive reaction to the HIV infection, hepatitis B & C, syphilis according to the history data
Severe eyesight and/or hearing disorders, serious articulation disorders and/or other deviations able to prevent the patient from adequate cooperation during the study)
Mental disorders in the history
Alcohol, drug abuse or drug dependence in the history
Patients which, according to the investigator, are obviously or probably incapable of understanding and evaluating this study information within the process of the informed consent form signing, including but not limited to with regard to expected risks and possible discomfort
Other diseases, symptoms or conditions not listed above, which, according to the investigator, are predicaments for the participation in the clinical study
The presence of contraindications for MRI
The presence of contraindications for taking the drug

Contraindications for MRI:

Electronic medical devices in the body (cardiomyostimulator and other)
Metal elements in the study area (prosthesis, clamp, fragment)
Invariable behavior of patients
Inability to remain still during MRI

Prohibited drugs/dietary supplements:

Ethyl methyl hydroxypyridine succinate and Meldonium (other than the one studied in the study)
Psychotropic medication
Drugs containing succinic acid and its salts
Drugs containing vitamin B6 and /or its derivatives
Antioxidants, antihypoxic drug and metabolic drugs
Nootropic drugs