Safety and Efficacy of Sequential Therapy With Mexidol® in Patients With Chronic Cerebral Ischemia (MEMO)

International Multicentre Randomized, Double-blind, Placebo-controlled Adaptive Design Clinical Trial to Evaluate the Safety and Efficacy of Sequential Therapy With Mexidol® Solution for Intravenous and Intramuscular Administration, 50 mg/ml (RPC PHARMASOFT LLC, Russia) and Mexidol® FORTE 250 Film-coated Tablets, 250 mg (RPC PHARMASOFT LLC, Russia) in Patients With Chronic Cerebral Ischemia (MEMO)

The purpose of this study is to evaluate safety and efficacy of sequential treatment with Mexidol® in patients with chronic cerebral ischemia (CCI).

Study Overview

• Status: Completed
• Conditions: Chronic Cerebral Ischemia
• Intervention / Treatment: Drug: Mexidol; Drug: Placebo

Detailed Description

Chronic cerebral ischemia (CCI) is a cerebral vascular pathology caused by slow progressive diffuse disruption of blood flow to the brain with gradually increasing defects in its functioning. The activation of lipid peroxidation with the release of large amounts of active oxygen radicals plays the key role in the pathogenesis of ischemic disorders, which leads to the development of oxidative stress. However, traditional drug therapy, which is aimed at improving blood flow to the brain, is mainly based on drugs with psychostimulant component, and does not always prevent the increase of oxidative damage to the patients' body. That is why it is necessary to search for drugs that would correct these processes selectively. Mexidol contains ethylmethylhydroxypyridine succinate as an active substance and may be the drug of choice for the treatment of CCI patients.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russia
  • Chelyabinsk, Russia, 454092
    • Municipal Autonomous Healthcare Insitution of the Order of the Red Banner of Labour "City Clinical Hospital No.1"
  • Ivanovo, Russia, 152040
    • Regional Budget Healthcare Institution "Ivanovo Regional Clinical Hospital"
  • Kazan', Russia, 420012
    • Federal State Budget Educational Institution of Higher Education "Kazan State Medical University"
  • Moscow, Russia, 125367
    • Federal State Budget Research Institution "Research Center of Neurology"
  • Moscow, Russia, 125445
    • Federal State Budget Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education"
  • Novosibirsk, Russia, 630054
    • State Budget Healthcare Institution of the Novosibirsk Region "City Hospital № 34"
  • Novosibirsk, Russia, 630117
    • Federal State Budget Research Institution "Federal Research Center for Fundamental and Translational Medicine"
  • Saint Petersburg, Russia, 194044
    • Federal State Budget Military Educational Institution of Higher Education "Military Medical Academy n.a. S.M.Kirov"
  • Sestroretsk, Russia, 197706
    • City Hospital No.40 of the Kurortny District
  • Voronezh, Russia, 394024
    • Private Healthcare Institution "Clinical Hospital "RR-Medicine" of Voronezh
  • Yaroslavl, Russia, 150000
    • OOO "Centre for Evidence-Based Medicine"
  • Yaroslavl, Russia, 150030
    • State Budget Healthcare Institution of the Yaroslavl Region "Clinical Hospital No.2"
  • Yekaterinburg, Russia, 620102
    • State Budget Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"
• Uzbekistan
  • Tashkent, Uzbekistan, 100187
    • Centre for Neurology and Neurorehabilitation n.a. N. M. Madzhido, OOO "Neyromed Servis"

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Patients of either sex aged from 40 to 90 years inclusive
2. MoCA scale score of 25 and lower
3. Patients meeting the criteria for the diagnosis: Mild (moderate) cognitive impairment when assessed by DSM-5.
4. Chronic Cerebral Ischemia (ICD-10 code 167.8)
5. Foci of leukoaraiosis or "silent" brain infarction documented by MRI/CT performed within the past 12 months.
6. Patients who signed an informed consent to the study participation
7. History of progressive multifocal or diffuse brain disease from 1 to 5 years
8. Patients receiving background therapy with a fixed dose and combination of drugs during the previous month, including (if indicated): antiplatelet therapy, therapy of cerebral atherosclerosis and arterial hypertension, ischemic heart disease or other chronic diseases.
9. Negative pregnancy test
10. Patients who have agreed to use a reliable method of contraception during the study participation until completion (for women of childbearing potential, including partners of study participants).
11. Patients who are able to understand all study requirements and who have consented to all the limitations imposed by the study

Exclusion Criteria:

1. Inclusion by mistake (overlooked inclusion or non-inclusion criteria)
2. Investigator's or Sponsor's decision to exclude a participant from the study due to a clinically significant protocol deviation/violation.
3. Serious adverse events or adverse events that do not meet the criteria for seriousness but may, in the investigator's opinion, be detrimental to the health or well-being of a participant if they continue participation in the study.
4. Any adverse event (which may be unrelated to the investigational drug) requiring observations, procedures, and/or medications not approved by the clinical trial protocol.
5. Participant's refusal to continue participation in the study or their lack of discipline
6. Allergic reaction to the investigational drug that requires cancelling the treatment
7. Participant's desire to terminate their participation early for any reason.
8. Loss of contact with the patient followed by failure to attend the visit.
9. The need to take therapies prohibited by this protocol: nootropic drugs, ethylmethylhydroxypyridine succinate, trimetazidine or meldonium, drugs affecting the function of the autonomic nervous system and other drugs that may, in the investigator's opinion, distort the study results.
10. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Main (Mexidol); Participants received Mexidol IV 500 mg (10 ml) once daily for 14 days, then Mexidol FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days	Drug: Mexidol; 50 mg/ml IV solution, 250 mg tablets; Other Names: Ethylmethylhydroxypyridine Succinate
Placebo Comparator: Control (Placebo); Participants received Mexidol Placebo matching Mexidol IV 500 mg (10 ml) once daily for 14 days, then Mexidol Placebo matching Mexidol FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days	Drug: Placebo; Placebo IV solution, Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0	The Montreal Cognitive Assessment (MoCA) is used to measure the degree of cognitive impairment in patients with CCI. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected after treatment.	Day 75+2 (Visit 5) compared with the baseline level (Visit 0, 7 days before treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4	The Montreal Cognitive Assessment (MoCA) is used to measure the changes in the severity of cognitive impairment at Visits 2 and 4 in comparison to Visit 0. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected.	Day 14 (Visit 2) and Day 44±2 (Visit 4) compared with the baseline level (Visit 0, 7 days before treatment)
Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health)	The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health)	The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20)	The Multidimensional Fatigue Inventory (MFI-20) is used between Visit 1 and Visits 2, 4, 5. MFI-20 is a 20-item self-administered questionnaire designed to measure fatigue in five four-item subscales: General fatigue, Physical fatigue, Reduced activity, Reduced motivation and Mental fatigue. 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.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Changes in the Anxiety Level According to the Beck Anxiety Inventory	The Beck Anxiety Inventory (BAI) consists of 21 self-reported items (four-point scale) used to assess the intensity of physical and cognitive anxiety symptoms during the past week. Scores may range from 0 to 63: minimal anxiety levels (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63).	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Autonomic Changes According to the A.M.Wein's Questionnaire	The A.M.Wein's questionnaire is used between Visit 1 and Visit 2, 4, 5. It includes 11 main signs of autonomic disorders. Each autonomic symptom is assessed using scores from 7 to 3, then the scores are summed. Scores may range from 0 to 60, higher scores mean a worse outcome. The total sum of the scores in healthy individuals should be 0-14 scores. 15-29 scores are indicative of moderate vegetative dystonia syndrome, 30 and more scores are indicative of severe vegetative dystonia syndrome.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test	The Digit Symbol Substitution Test is used between Visit 1 and Visits 2, 4, 5. The DSST is used to measure attention, processing speed and executive function. It is a pencil and paper test of psychomotor performance in which the subject is given a key grid of numbers and matching symbols and a test section with numbers and empty boxes. The test consists of filling as many empty boxes as possible with a symbol matching each number. The score is the number of correct number-symbol matches achieved in 90 s. Scores range from 0 to 100, with higher scores indicating higher cognitive function.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Motor Changes Assessed With the Tinetti Test	The Tinetti test is used between Visit 1 and Visits 2, 4, 5. The Tinetti test is a clinical test for the assessment of balance and gait. It has a gait score and a balance score using a 3-point ordinal scale of 0, 1 and 2. Gait is scored over 12 and balance is scored over 16 totalling 28. The lower the score on the Tinetti test, the higher the risk of falling. Tinetti test score equal or less than 18 shows high risk of fall, 19-23 scores show moderate risk of fall, and score equal or higher than 24 shows low risk of fall. Thus, min value is 0, max value is 28, higher scores mean a better outcome.	Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure	The Clinical Global Impressions Scale is a standardized assessment tool used to rate the severity of illness, change over time, and efficacy of medication. The interpretation of scores is as follows: 00 - Not assessed 01 - Vast improvement. Side effects - None. 03 - Vast improvement. Side effects - Significantly interfere with patient's therapeutic patient's functioning 04 - Vast improvement. Side effects - outweights therapeutic effect 05 - Decided improvement. Side effects - none 09 - Slight improvement. Side effects - none 10 - Slight improvement. Side effects - do not significantly interfere with patient's functioning 13 - Slight improvement. Side effects - none	Day 75+2 (Visit 5)

Collaborators and Investigators

• Sponsor: Pharmasoft
• Investigators: Principal Investigator: Alina S. Agafina, MD, Cand.Med.Sci, Saint Petersburg State Budget Healthcare Institution "City Hospital No.40 of the Kurortny District"; Principal Investigator: Elena V. Vostrikova, MD, Cand.Med.Sci, State Budget Healthcare Institution of the Nivisibirsk Region "City Hospital No.34"; Principal Investigator: Andrey M. Alasheev, MD, Dr.Med.Sci, State Budget Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"; Principal Investigator: Marine M. Tanashyan, Prof., Dr.Med.Sci, Federal State Budget Research Institution "Research Center of Neurology"; Principal Investigator: Min G. Omelyanenko, MD, Dr.Med.Sci, Regional Budget Healthcare Institution "Ivanovo Regional Clinical Hospital"; Principal Investigator: Stanislav O. Pozdnyakov, MD, Cand.Med.Sci, OOO "Centre for Evidence-Based Medicine"; Principal Investigator: Aleksandr Y. Malygin, MD, Dr.Med.Sci, State Budget Healthcare Institution of the Yaroslavl Region "Clinical Hospital No.2"; Principal Investigator: Aida A. Yakupova, MD, Cand.Med.Sci, Federal State Budget Educational Institution of Higher Education "Kazan State Meical University"; Principal Investigator: Igor V. Litvinenko, Prof., Dr.Med.Sci, Federal State Budget Military Educational Institution of Higher Education "Military Medical Academy n.a. S.M.Kirov"; Principal Investigator: Irina G. Lukashevich, MD, Municipal Autonomous Healthcare Insitution of the Order of the Red Banner of Labour "City Clinical Hospital No.1"; Principal Investigator: Olga A. Sinitsyna, MD, Cand.Med.Sci, State Budget Healthcare Institution of the Yaroslavl Region "Clinical Hospital No.2"; Principal Investigator: Larisa A. Shchepankevich, MD, Dr.Med.Sci, Federal State Budget Research Institution "Federal Research Center for Fundamental and Translational Medicine"; Principal Investigator: Galina A. Batishcheva, Prof., Dr.Med.Sci, Private Healthcare Institution "Clinical Hospital "RR-Medicine" of Voronezh; Principal Investigator: Olga D. Ostroumova, Prof., Dr.Med.Sci, Federal State Budget Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education"; Principal Investigator: Yokutkhon N. Madzhidova, Prof., Dr.Med.Sci, Centre for Neurology and Neurorehabilitation n.a. N.M.Madzhido, OOO "Neyromed Servis"

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): December 8, 2020
• Study Completion (Actual): December 8, 2020

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Cognitive Impairment; Ischemia; Oxidative Stress; Brain; Neuroprotection; Central Nervous System; Cognitive; Cerebrovascular Disorders; Neurological Rehabilitation; Neurobehavioral Manifestations; Neurodegenerative; Cerebral; Central Nervous System Disorders; Cerebral Hypoxia; CCI; Stroke Recovery; Post-stroke Cognitive Impairment; Mexidol; Ethylmethylhydroxypyridine Succinate; Chronic Cerebral Ischemia; Antioxidant Therapy; Chronic Brain Hypoxia; Neurodegenerative Processes; Oxidative Stress Reduction; Energy Metabolism Enhancement
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Signs and Symptoms, Respiratory; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Ischemia; Cognitive Dysfunction; Central Nervous System Diseases; Neurobehavioral Manifestations; Cerebrovascular Disorders; Hypoxia, Brain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Psychotropic Drugs; Antioxidants; Protective Agents; emoxypine succinate; ethylmethylhydroxypyridine succinate
• Other Study ID Numbers: MexidolMEMO2020; PHS-CICADIS-005-MEX-SOL-TAB (Other Identifier: Pharmasoft)

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
• product manufactured in and exported from the U.S.: No