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

Primary Purpose

Asthenia, COVID-19, Functional MRI

Status
Completed
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Structural and functional MRI
Ethyl methyl hydroxypyridine succinate + Meldonium
Placebo
Sponsored by
Promomed, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthenia focused on measuring Asthenia, COVID-19, Chronic fatigue syndrome, Functional MRI, Cognitive impairment, Brain fog, BRAINMAX

Eligibility Criteria

25 Years - 50 Years (Adult)All SexesDoes not accept 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

Sites / Locations

  • Federal State Budgetary Research Institution "Research Centre of Neurology"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

fMRI with subsequent injection of placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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

Full Information

First Posted
July 10, 2023
Last Updated
July 11, 2023
Sponsor
Promomed, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05939622
Brief Title
Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
May 18, 2022 (Actual)
Primary Completion Date
December 20, 2022 (Actual)
Study Completion Date
December 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Promomed, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthenia, COVID-19, Functional MRI, Cognitive Impairment
Keywords
Asthenia, COVID-19, Chronic fatigue syndrome, Functional MRI, Cognitive impairment, Brain fog, BRAINMAX

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
fMRI with subsequent injection of active drug (Ethyl methyl hydroxypyridine succinate + Meldonium)
Arm Type
Experimental
Arm Description
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
Arm Title
fMRI with subsequent injection of placebo
Arm Type
Placebo Comparator
Arm Description
Arm 2 (n=15) performed structural and functional MRI and received Placebo in the same way.
Intervention Type
Other
Intervention Name(s)
Structural and functional MRI
Other Intervention Name(s)
fMRI
Intervention Description
MRI using a Siemens MAGNETOM Prisma 3T scanner before and after a course of therapy, using resting state fMRI and with cognitive paradigm.
Intervention Type
Drug
Intervention Name(s)
Ethyl methyl hydroxypyridine succinate + Meldonium
Other Intervention Name(s)
BRAINMAX®
Intervention Description
Ethyl methyl hydroxypyridine succinate 100.0 mg/mL, meldonium dihydrate - 100.0 mg/mL (Solution for intravenous and intramuscular administration)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo was used in the same way
Primary Outcome Measure Information:
Title
Changing patterns of brain activation using task fMRI with a cognitive paradigm
Description
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.
Time Frame
From baseline to Visit 2 (day 10)
Secondary Outcome Measure Information:
Title
Asthenia on a scale Multidimensional Fatigue Inventory (MFI-20) after the completion of the parenteral therapy
Description
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
Time Frame
From baseline to Visit 2 (day 10)
Title
Fatigue on a Fatigue Assessment Scale (FAS-10) scale after the completion of the parenteral therapy
Description
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
Time Frame
From baseline to Visit 2 (day 10)
Title
Cognitive function on a Montreal Cognitive Assessment (MoCA) scale after the completion of the parenteral therapy
Description
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
Time Frame
From baseline to Visit 2 (day 10)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marine Tanashyan, MD, PhD
Organizational Affiliation
Federal State Budgetary Research Institution "Research Centre of Neurology"
Official's Role
Principal Investigator
Facility Information:
Facility Name
Federal State Budgetary Research Institution "Research Centre of Neurology"
City
Moscow
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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