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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Asthenia; Cognitive Impairment; Functional MRI
• Intervention / Treatment: Drug: Placebo; Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Federal State Budgetary Research Institution "Research Centre of Neurology"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: Placebo; Placebo was used 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing patterns of brain activation using task fMRI with a cognitive paradigm	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.	From baseline to Visit 2 (day 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the parenteral therapy	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	From baseline to Visit 2 (day 10)
Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the parenteral therapy	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	From baseline to Visit 2 (day 10)
Cognitive function on a Montreal Cognitive Assessment (MoCA) scale after the completion of the parenteral therapy	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	From baseline to Visit 2 (day 10)

Collaborators and Investigators

• Sponsor: Promomed, LLC
• Investigators: Principal Investigator: Marine Tanashyan, MD, PhD, Federal State Budgetary Research Institution "Research Centre of Neurology"

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Cognitive impairment; Functional MRI; Chronic fatigue syndrome; Brain fog; Asthenia; BRAINMAX
• Additional Relevant MeSH Terms: Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; Cognition Disorders; COVID-19; Cognitive Dysfunction; Asthenia; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; 3-(2,2,2-trimethylhydrazine)propionate
• Other Study ID Numbers: BRAINMAX_2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No