The primary objective of this study is to evaluate the efficacy of Mexidol® sequential parenteral and oral administration as part of comprehensive therapy in older adults with chronic brain ischemia and vascular cognitive impairment, no dementia (VCIND).
This is a pilot, open-label, prospective, randomized, comparative, controlled study in parallel groups designed to evaluate the efficacy and safety of sequential Mexidol® therapy used in addition to standard therapy in older adults with chronic brain ischemia and vascular cognitive impairment, no dementia (VCIND). The study included 120 participants randomized into two groups: * Group 1 received standard therapy combined with Mexidol® solution (500 mg once daily, IV infusion) for the first 5 days, followed by Mexidol® FORTE 250 tablets (250 mg three times daily) for 60 days. * Group 2 received standard therapy only. Within each treatment group, a pre-specified subgroup analysis was performed based on the presence or absence of frailty, followed by a comparative analysis of the secondary outcome measures for each subgroup.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
In addition to standard therapy, Mexidol sequential therapy was administered in two phases: * Days 1 to 5: Intravenous (IV) infusion of 10 mL (500 mg) once daily, diluted in 100-150 mL of 0.9% sodium chloride solution. Infusion rate: 40-60 drops per minute. * Days 6 to 65: Oral administration of Mexidol® FORTE 250 mg tablets, 1 tablet 3 times daily (750 mg total daily dose) for 60 consecutive days.
Standard background therapy administered in accordance with institutional protocols and applicable clinical guidelines, including cognitive training.
Ivanovo Regional Clinical Hospital
Ivanovo, Russia
Medinet, LLC
Saint Petersburg, Russia
City Hospital № 40 of Kurortny District
Saint Petersburg, Russia
Vsevolozhsk Clinical Interdistrict Hospital
Vsevolozhsk, Russia
Change in the Montreal Cognitive Assessment (MoCA) Total Score at Visit 4 compared to Visit 0 by treatment groups
The Montreal Cognitive Assessment (MoCA) is a 30-point validated scale that covers multiple cognitive domains including spatiotemporal orientation, sustained attention, visuospatial function, executive function, verbal memory, language, naming, and abstract thinking \[30-point scale: min value 0, max value 30, higher scores mean a better outcome\].
Time frame: Visit 0 (Baseline, Day -4 to Day 0) and Visit 4 (Day 65±2 days)
Change in the Montreal Cognitive Assessment (MoCA) Total Score at Visit 2 compared to Visit 1
The Montreal Cognitive Assessment (MoCA) is a 30-point validated scale that covers multiple cognitive domains including spatiotemporal orientation, sustained attention, visuospatial function, executive function, verbal memory, language, naming, and abstract thinking \[30-point scale: min value 0, max value 30, higher scores mean a better outcome\]. Note: Per protocol, the MoCA assessment is performed at Visit 0 (Screening). For patients where Visit 1 (Randomization) and Visit 0 do not coincide, the screening data are used as the baseline values for Visit 1.
Time frame: Visit 1 / Visit 0 (Baseline, Day -4 to Day 1) and Visit 2 (Day 5)
Change in the Clinical Global Impression (CGI) Scale Scores at Visit 2 Compared to Visit 1, Including Severity of Illness, Global Clinical Change, and Efficacy Index
The Clinical Global Impression (CGI) scale is a 3-item observer-rated scale used to evaluate illness severity, global improvement or change, and treatment response. It consists of three independent subscales, each rated separately: CGI-Severity (CGI-S) rates the severity of illness on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients); CGI-Improvement (CGI-I) rates the patient's change over time on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse); CGI-Efficacy Index is a 4x4 rating scale that assesses the therapeutic effect and treatment-related adverse events. Scores range from 00 (not assessed) or 01 (marked improvement and no side effects) to 16 (unchanged or worse and side effects outweigh the therapeutic effects). A lower score reflects a better therapeutic index.
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Time frame: Visit 1 (Day 1) and Visit 2 (Day 5)
Change in the Beck Anxiety Inventory (BAI) Total Score at Visit 2 compared to Visit 1
The Beck Anxiety Inventory (BAI) consists of 21 self-report items (scored on a 4-point scale) used to assess the severity of physical and cognitive anxiety symptoms during the past week. Total scores range from 0 to 63: minimal anxiety (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63). \[Scale range: 0 to 63; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 2 (Day 5)
Change in the Mini-Mental State Examination (MMSE) Total Score at Visit 4 compared to Visit 0
The Mini-Mental State Examination (MMSE) is a 30-point questionnaire of global cognitive status that assesses five key areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Total scores range from 0 to 30, with higher scores indicating better cognition. A score of 24 or more indicates normal cognition. Scores below 24 indicate cognitive impairment, categorized as mild (19-23 points), moderate (10-18 points), or severe (≤9 points) \[30-point scale: min value 0, max value 30, higher scores mean a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Lawton Instrumental Activities of Daily Living (IADL) Scale Total Score at Visit 4 compared to Visit 1
The Lawton Instrumental Activities of Daily Living (IADL) Scale is an 8-item instrument used to assess independent living skills and complex occupational performance. The scale evaluates 8 functional domains: ability to use telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medications, and ability to handle finances. Each item is scored as either 0 (dependent) or 1 (independent). The total score is calculated as the sum of all 8 domains ranging from 0 to 8. A score of 0 represents low functioning (maximum dependence) and a score of 8 represents high functioning (full independence) \[Scale range: 0 to 8; higher scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Barthel Index (BI) for Activities of Daily Living Total Score at Visit 4 compared to Visit 1
The Barthel Index (BI) for Activities of Daily Living is a validated 10-item clinician- or caregiver-reported rating scale used to assess a patient's performance and level of independence in basic activities of daily living (ADL) and mobility. The index evaluates 10 functional domains: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility, and stairs. Items are scored in increments of 5. The total score is calculated as the sum of all 10 items, ranging from 0 to 100. A score of 0 represents complete dependence, while a score of 100 represents complete independence. \[Scale range: 0 to 100; higher scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Short Physical Performance Battery (SPPB) Total Score at Visit 4 compared to Visit 1
The Short Physical Performance Battery (SPPB) is a standardized assessment tool used to evaluate lower extremity function and mobility in older adults. It consists of three objective subtests designed to mimic everyday physical demands: a 4-meter walk to assess gait speed, a repeated chair stand test (rising from a seated position 5 times) to assess lower limb strength, and three 10-second static balance tests in different foot positions (side-by-side, semi-tandem, and tandem). Each of the three subtests is scored from 0 to 4, resulting in a total summary score ranging from 0 to 12. Lower scores indicate poorer physical function and higher disability, while higher scores indicate better lower extremity performance and functional independence. \[Scale range: 0 to 12; higher scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Digit Symbol Substitution Test (DSST) Total Score at Visit 4 compared to Visit 0
The Digit Symbol Substitution Test (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.
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Multidimensional Fatigue Inventory (MFI-20) Total Score at Visit 4 compared to Visit 1
The Multidimensional Fatigue Inventory (MFI-20) is a 20-item self-administered questionnaire designed to measure fatigue in five 4-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.
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Beck Anxiety Inventory (BAI) Total Score at Visit 4 compared to Visit 1
The Beck Anxiety Inventory (BAI) consists of 21 self-report items (scored on a 4-point scale) used to assess the severity of physical and cognitive anxiety symptoms during the past week. Total scores range from 0 to 63: minimal anxiety (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63). \[Scale range: 0 to 63; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Tinetti Gait and Balance Test Total Score at Visit 4 compared to Visit 1
The Tinetti Gait and Balance 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 totaling 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. Min value is 0, max value is 28, higher scores mean a better outcome.
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the 36-Item Short Form Survey (SF-36) Total Score at Visit 4 compared to Visit 1
The 36-Item Short Form Health Survey (SF-36) 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 a better health status, and a mean score of 50 represents a normative value for all scales. \[Scale range: 0 to 100; higher scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Clinical Global Impression (CGI) Scale Scores at Visit 4 Compared to Visit 1, Including Severity of Illness, Global Clinical Change, and Efficacy Index
The Clinical Global Impression (CGI) scale is a 3-item observer-rated scale used to evaluate illness severity, global improvement or change, and treatment response. It consists of three independent subscales, each rated separately: CGI-Severity (CGI-S) rates the severity of illness on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients); CGI-Improvement (CGI-I) rates the patient's change over time on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse); CGI-Efficacy Index is a 4x4 rating scale that assesses the therapeutic effect and treatment-related adverse events. Scores range from 00 (not assessed) or 01 (marked improvement and no side effects) to 16 (unchanged or worse and side effects outweigh the therapeutic effects). A lower score reflects a better therapeutic index.
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Morse Fall Scale (MFS) Total Score at Visit 4 compared to Visit 1
The Morse Fall Scale (MFS) is a validated 6-item clinician-reported tool used to assess a participant's risk of falling. It evaluates six variables: history of falling, secondary diagnosis, ambulatory aid, intravenous therapy, gait/transferring, and mental status. The total score is calculated as the sum of all items, ranging from 0 to 125. Scores are stratified into low risk (0-24), moderate risk (25-44), and high risk (≥45) of falling. \[Scale range: 0 to 125; higher scores indicate a worse outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Falls Risk Self-Assessment Scale Total Score at Visit 4 compared to Visit 1
The Falls Risk Self-Assessment Scale is a 12-item self-administered questionnaire used to evaluate a participant's perceived risk of falling. For each question, a "no" answer is scored as 0 points, while a "yes" answer is scored as either 1 or 2 points, depending on the item weight. The total score is calculated as the sum of all 12 items. Total scores are interpreted as follows: a score of less than 4 points indicates a low risk of falling, and a score of 4 or more points indicates a high risk of falling. \[Scale range: 0 to 14; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in the Insomnia Severity Index (ISI) Total Score at Visit 4 compared to Visit 1
The Insomnia Severity Index (ISI) is a 7-item self-administered instrument used to assess the nature, severity, and impact of sleep disturbances experienced over the past 2 weeks. Individual items are rated on a 5-point Likert scale (0 to 4), with the total score calculated as the sum of all 7 items, ranging from 0 to 28. Total scores are interpreted as follows: no clinically significant insomnia (0-7 points), subthreshold insomnia (8-14 points), clinical insomnia of moderate severity (15-21 points), and severe clinical insomnia (22-28 points). \[Scale range: 0 to 28; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in Time to Complete the Trail Making Test Part A (TMT-A) at Visit 4 compared to Visit 1
The Trail Making Test Part A (TMT-A) is a neuropsychological instrument used to assess visual search, scanning, speed of processing, and executive function. Participants are required to connect a set of 25 encircled numbers in numerical order as rapidly as possible. Performance is scored based on the total time taken to complete the task, where each second equals 1 point. A higher score (longer completion time) indicates cognitive impairment, while a lower score indicates better cognitive performance and faster processing speed. \[Scale range: not applicable; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Change in Time to Complete the Trail Making Test Part B (TMT-B) at Visit 4 compared to Visit 1
The Trail Making Test Part B (TMT-B) is a neuropsychological instrument used to assess visual search, scanning, speed of processing, cognitive flexibility, and executive function. Participants are required to connect a set of 25 encircled numbers and letters, alternating between numerical and alphabetical order (e.g., 1-A-2-B) as rapidly as possible. Performance is scored based on the total time taken to complete the task, where each second equals 1 point. A higher score (longer completion time) indicates cognitive impairment, while a lower score indicates better cognitive performance. \[Scale range: not applicable; lower scores indicate a better outcome\].
Time frame: Visit 1 (Day 1) and Visit 4 (Day 65±2 days)
Assessment of Safety
Total number of adverse events (AEs), stratified by severity and frequency; Incidence of adverse drug reactions (ADRs); Incidence of serious adverse events (SAEs) related to the investigational product; Proportion of participants with at least one reported AE; Proportion of participants who discontinued treatment due to AEs. Note: All clinically significant deviations in patient health status (based on physical examination, laboratory, and instrumental assessments) from baseline screening data and reference ranges were recorded as adverse events. Adverse medical events detected during the screening period were classified as medical history (pre-existing/concomitant conditions).
Time frame: From Day 1 (Visit 1) to Day 65 (Visit 4)