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NCT Number: NCT05247125

The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)

There is a lack of complex studies which could establish the association between genetic circadian factors with the features and short-term outcomes of ischemic stroke, as well as the effects of various auxiliary therapies for circadian rhythm modulation for neuroplasticity enhancement and improvement of short-term outcomes in ischemic stroke.

The main research hypothesis is that circadian factors influence the recovery from ischemic stroke via sleep-mediated regulation of synaptic plasticity.

The project aims at the investigation of the influence of combined melatonin therapy and blue light exposure on molecular circadian biomarkers, sleep characteristics, neuroplasticity markers and stroke outcome in acute stroke patients.

This study is a prospective, interventional, randomized placebo-controlled trial.

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Key information

Conditions

Ischemic Stroke, Acute Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Chronobiology Disorders Dyssomnias Ischemic Stroke Mental Disorders Nervous System Diseases Occupational Diseases Sleep Disorders, Circadian Rhythm Sleep Wake Disorders Stroke Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Almazov National Medical Research Centre

Saint Petersburg, 197341, Russia

Location status: Recruiting

Location contact

Lyudmila Korostovtseva

CONTACT

[email protected]

89217873548

About this study

The study will investigate the influence of combined blue light exposure and melatonin therapy on molecular biomarkers of circadian rhythms, sleep characteristics and stroke outcome in acute stroke patients This study is designed as a prospective study in acute stroke patients (approx 80 patients) admitted to the Stroke Unit. After initial assessment, the participants will be randomly assigned in 4 groups (the treatment or control) with approx.20 participants in each group.

In all participants, the following parameters will be assessed: medical records, stroke characteristics, sleep characteristics, cardiovascular circadian rhythms and blood samples for the evaluation of circadian molecular biomarkers at baseline and 14 days after inclusion. Stroke outcomes will be reassessed at 3-month follow-up.

The following associations will be assessed:

  • the role of blue light exposure and melatonin treatment for stroke outcome
  • the role of blue light exposure and melatonin treatment in the modulation of sleep parameters in acute stroke
  • the association of molecular biomarkers of circadian rhythms with stroke outcome (the difference in neurological and functional deficit from admission to 14 and 90 days after study inclusion), with stroke characteristics (stroke subtype and neuroimaging stroke parameters, routine protocol) and with sleep characteristics.
  • the association of sleep characteristics with stroke outcome (the difference in neurological and functional deficit from admission to 14 and 90 days after stroke) and with stroke characteristics (stroke subtype and neuroimaging stroke parameters, routine protocol).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • acute (symptom onset to admission <1 days) ischemic stroke
  • ischemic stroke affecting the branches of anterior cerebral artery, middle cerebral artery and posterior cerebral artery
  • age 18-80 years
  • moderate or severe stroke (National Institutes of Health Stroke Scale, NIHSS>=5)
  • intravascular stroke treatment with thrombolysis or thrombectomy leading to satisfactory reperfusion (if applicable)
  • informed consent

Exclusion criteria

  • secondary parenchymal hemorrhage (>hemorrhage index (HI)-2)
  • clinically unstable or life-threatening conditions
  • previous stroke in the last 6 months
  • known progressive neurological diseases
  • known psychiatric diseases
  • concomitant benzodiazepine medication
  • drug or alcohol abuse
  • pregnancy
  • inability to participate in the study
  • severe sensory aphasia
  • melatonin intake at/before admission
  • light therapy use at/before admission
  • blindness
  • severe sleep-disordered breathing (apnea-hypopnea index >=30/h)
  • contraindications to light therapy (severe retinopathy, epilepsy, porphyria, intake of drugs with photosensitizing effects)
  • contraindications to melatonin intake (severe bronchial asthma, severe autoimmune disorders, chronic kidney disease 3b stage and higher, leukosis)
  • congestive heart failure with reduced ejection fraction (<=45%) or New York Heart Association (NYHA) classification III-IV functional class.

Treatment and study plan

Blue light exposure + Melatonin treatment

Combination Product

3 mg Melatonin pill will be given 1 hour before going to bed. Blue light exposure will be performed during 30-minute sessions with the use of the lamps (Lumie/Vitamin L) in the morning.

Melatonin treatment

Drug

3 mg Melatonin pill will be given 1 hour before going to bed.

Other names: Melaxen

Blue light exposure

Device

Blue light exposure will be performed during 30-minute sessions with the use of the lamps (Lumie/Vitamin L) in the morning.

Other names: Lamps Lumie/Vitamin L

Placebo

Combination Product

Placebo light exposure will be performed by using lamp turned off; and placebo pill will be given in the evening

Primary outcomes

  1. Change in the value of National Institutes of Health Stroke Scale from baseline to 14 days after inclusion

    Time frame: From baseline to 14 days after treatment initiation

    National Institutes of Health Stroke Scale (NIHSS) is a tool used to objectively quantify the impairment caused by a stroke, 0-42 scores, higher scores characterize worse impairment

  2. Stroke-related disability assessed by the change in modified Rankin scale from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    values of modified Rankin scale (scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke, from 0 (no symptoms) to 6 (dead) points)

  3. Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Rivermead Mobility Index (a standardized scale used to assess mobility in patients with neurological deficits, a maximum of 15 points is possible; higher scores indicate better mobility performance)

  4. Stroke-related disability assessed by the change in Barthel Index from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Barthel Index (a common scale used to measure performance in activities of daily living, 0-100 scores, higher scores define better performance)

Secondary outcomes

  1. Change in Psychomotor vigilance task (mean reaction time) from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    The psychomotor vigilance task is a sustained-attention, reaction-timed task that measures the speed with which subjects respond to a visual stimulus, the outcome (mean reaction time) is measured in msec

  2. Change in Psychomotor vigilance task (mean reaction time) from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    The psychomotor vigilance task is a sustained-attention, reaction-timed task that measures the speed with which subjects respond to a visual stimulus, the outcome (mean reaction time) is measured in msec

  3. Change in Kraepelin test from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Kraepelin test is the test in which the examinee performs a simple single-digit addition. The outcome is the number of correct and incorrect addition operations per each 30 sec and during the whole task, performance index (number of correct addition operations during second part of task / number of correct addition operations during first part of task)

  4. Change in Kraepelin test from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Kraepelin test is the test in which the examinee performs a simple single-digit addition. The outcome is the number of correct and incorrect addition operations per each 30 sec and during the whole task, performance index (number of correct addition operations during second part of task / number of correct addition operations during first part of task)

  5. Change in Trail Making test from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. It can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning

  6. Change in Trail Making test from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. It can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. Execution time will be assessed (in msec)

  7. Change in Victoria Stroop test from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Victoria Stroop is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference. Execution time will be measured. (in msec)

  8. Change in Victoria Stroop test from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 day after inclusion

    Victoria Stroop is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference. Execution time will be measured. (in msec)

  9. Change in Hopkins Verbal Learning Test (Revised) from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Hopkins Verbal Learning Test - Revised brief assessment of immediate recall, delayed recall and delayed recognition. The number of words recalled will be assessed.

  10. Change in Hopkins Verbal Learning Test (Revised) from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Hopkins Verbal Learning Test - Revised brief assessment of immediate recall, delayed recall and delayed recognition. The number of words recalled will be assessed.

  11. Change in Brief Visuospatial Memory Test (Revised) from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Brief Visuospatial Memory Test (Revised)is a commonly used, commercialized, assessment tool to measure visuospatial learning and memory abilities across research and clinical settings. The number of figures will be assessed.

  12. Change in Brief Visuospatial Memory Test (Revised) from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Brief Visuospatial Memory Test (Revised)is a commonly used, commercialized, assessment tool to measure visuospatial learning and memory abilities across research and clinical settings. The number of figures will be assessed.

  13. Change in Wechsler Memory Scale (Revised) from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    Wechsler Memory Scale - Revised is a neuropsychological test designed to measure different memory functions in a person. A composite score will be assessed.

  14. Change in Wechsler Memory Scale (Revised) from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Wechsler Memory Scale - Revised is a neuropsychological test designed to measure different memory functions in a person. A composite score will be assessed.

  15. Change in Corsi block-tapping test from baseline to 14 days after treatment initiation

    Time frame: From baseline to 14 days after treatment initiation

    The Corsi block-tapping test is a psychological test that assesses visuo-spatial short term working memory. The visual span raw score will be assessed.

  16. Change in Corsi block-tapping test from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    The Corsi block-tapping test is a psychological test that assesses visuo-spatial short term working memory. The visual span raw score will be assessed.

  17. Change from baseline in objective sleep duration assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    Sleep duration (minutes)

  18. Change from baseline in objective sleep efficiency assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    sleep efficiency (%)

  19. Change from baseline in objective sleep latency assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    sleep latency (minutes)

  20. Change from baseline in sleep S1 stage duration assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    S1 sleep stage percentage of total sleep time (%)

  21. Change from baseline in sleep S2 stage duration assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    S2 sleep stage percentage of total sleep time (%)

  22. Change from baseline in sleep S3 stage duration assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    S3 sleep stage percentage of total sleep time (%)

  23. Change from baseline in rapid eye movement (REM) sleep stage duration assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    Rapid eye movement (REM) sleep stage percentage of total sleep time (%)

  24. Change from baseline in wake-after-sleep-onset time assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    wake after sleep onset time (minutes)

  25. Change from baseline in arousal index assessed by polysomnography

    Time frame: From baseline to 14 days after treatment initiation

    Arousal index (episodes/hour of sleep)

  26. Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 90 days after inclusion

    Time frame: from baseline to 14 days after treatment initiation

    Hospital anxiety and depression scale is used to determine the levels of anxiety and depression. It is a 14-item scale; Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression, higher scores indicate worse situation

  27. Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 14 days after treatment initiation

    Time frame: From baseline to 90±7 days after inclusion

    Hospital anxiety and depression scale is used to determine the levels of anxiety and depression. It is a 14-item scale; Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression, higher scores indicate worse situation

  28. Assessment of mood by change in Visual Analogue Mood Scale from baseline to 14 days after treatment initiation

    Time frame: from baseline to 14 days after treatment initiation

    Visual Analogue Mood Scale is a reliable and valid measure of eight specific mood states: Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense. The score for each mood ranges from 0 to 100 (100 mm vertical line), with 100 representing a maximal level of that mood and zero representing a minimal level (or absence) of that mood

  29. Assessment of mood by change in Visual Analogue Mood Scale from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Visual Analogue Mood Scale is a reliable and valid measure of eight specific mood states: Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense. The score for each mood ranges from 0 to 100 (100 mm vertical line), with 100 representing a maximal level of that mood and zero representing a minimal level (or absence) of that mood

  30. Change in the value of National Institutes of Health Stroke Scale from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    National Institutes of Health Stroke Scale (NIHSS) is a tool used to objectively quantify the impairment caused by a stroke, 0-42 scores, higher scores characterize worse impairment

  31. Change in modified Rankin scale from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    values of modified Rankin scale (scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke, from 0 (no symptoms) to 6 (dead) points)

  32. Change in Rivermead Mobility Index from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Rivermead Mobility Index (a standardized scale used to assess mobility in patients with neurological deficits, a maximum of 15 points is possible; higher scores indicate better mobility performance)

  33. Change in Barthel Index from baseline to 90 days after inclusion

    Time frame: From baseline to 90±7 days after inclusion

    Barthel Index (a common scale used to measure performance in activities of daily living, 0-100 scores, higher scores define better performance)

Other outcomes

  1. Change from baseline in time in bed assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    time in bed (minutes)

  2. Change from baseline in total sleep time assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    total sleep time (minutes)

  3. Change from baseline in sleep efficiency assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    sleep efficiency (%)

  4. Change from baseline in sleep onset latency assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    sleep onset latency (min)

  5. Change from baseline in number of awakenings assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    number of awakenings

  6. Change from baseline in mean motor activity assessed by actigraphy

    Time frame: from baseline to 14 days after treatment initiation

    mean motor activity (units)

  7. Change from baseline in Sleep Quality Score assessed by questionnaire Pittsburgh Sleep Quality Index

    Time frame: from baseline to 14 days after treatment initiation

    Pittsburgh Sleep Quality Index is a self-rated questionnaire which assesses subjective sleep quality and disturbances over a 1-month time interval, Each of the sleep components yields a score ranging from 0 to 3, with 3 indicating the greatest dysfunction. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score indicating worse sleep quality

  8. Change from baseline in daytime sleepiness assessed by Epworth Sleepiness Scale

    Time frame: from baseline to 14 days after treatment initiation

    Epworth Sleepiness Scale is a common tool to assess sleepiness; 0-24 points, higher score indicate greater sleepiness

  9. Change from baseline in fatigue severity assessed by Fatigue severity Scale

    Time frame: from baseline to 14 days after treatment initiation

    Fatigue severity Scale is a common 9-item tool used to determine and quantify fatigue as subjective feeling of exhaustion, persisting lack of energy and rapid inanition, 9-63 points, higher score indicates more severe fatigue

  10. Change from baseline in Insomnia severity index

    Time frame: from baseline to 14 days after treatment initiation

    Insomnia severity index is a 7-item tool to assess the severity of insomnia, 0-5 points per each item, higher score indicates more severe insomnia

  11. Change from baseline in sensorimotor assessment of upper limbs

    Time frame: from baseline to 14 days after treatment initiation

    Sensorimotor assessment of upper limbs by Fugl-Meyer is a stroke-specific, performance-based impairment index. The total possible scale score is 226

  12. Change from baseline in melatonin curve secretion

    Time frame: from baseline to 14 days after treatment initiation

    salivary melatonin levels samples collected every 3 hours for 24 hours at study inclusion and at 14 days after study inclusion

  13. Change from baseline in cortisol curve secretion

    Time frame: from baseline to 14 days after treatment initiation

    salivary cortisol sampled every 3 hours for 24 hours at study inclusion and at 14 days after study inclusion

  14. Change from baseline in circadian brain-derived neurotrophic factor messenger ribonucleic acid (mRNA) expression

    Time frame: from baseline to 14 days after treatment initiation

    Brain-derived neurotrophic factor messenger ribonucleic acid (mRNA) expression will be measured in blood samples taken every 4 hours for 24 hours at study inclusion and at 14 days after study inclusion

  15. Change from baseline in circadian clock gene CLOCK messenger ribonucleic acid (mRNA) expression

    Time frame: from baseline to 14 days after treatment initiation

    clock gene CLOCK messenger ribonucleic acid (mRNA) expression will be measured in blood samples taken every 4 hours for 24 hours at study inclusion and at 14 days after study inclusion

  16. Change from baseline in circadian clock gene Bmal1 messenger ribonucleic acid (mRNA) expression

    Time frame: from baseline to 14 days after treatment initiation

    clock gene Bmal1 messenger ribonucleic acid (mRNA) expression will be measured in blood samples taken every 4 hours for 24 hours at study inclusion and at 14 days after study inclusion

  17. Change from baseline in circadian Melatonin receptor messenger ribonucleic acid (mRNA) expression

    Time frame: from baseline to 14 days after treatment initiation

    Melatonin receptor messenger ribonucleic acid (mRNA) expression will be measured in blood samples taken every 4 hours for 24 hours at study inclusion and at 14 days after study inclusion

  18. Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 14 days

    Time frame: from baseline to 14 days after treatment initiation

    heart rate variability assessed by electrocardiogram (maximum heart rate - minimum heart rate, beats per minute)

  19. Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 90 days after inclusion

    Time frame: from baseline to 90±7 days after inclusion

    heart rate variability assessed by electrocardiogram (maximum heart rate - minimum heart rate, beats per minute)

  20. Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method - from baseline to 14 days

    Time frame: from baseline to 90±7 days after treatment initiation

    respiratory movement amplitude assessed by respiratory rate abdominal and thoracic sensors (units)

  21. Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method- from baseline to 90 days

    Time frame: from baseline to 90±7 days after inclusion

    respiratory movement amplitude assessed by respiratory rate abdominal and thoracic sensors (units)

  22. Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation

    Time frame: from baseline to 14 days after treatment initiation

    alpha rhythm index (%) assessed by electroencephalogram

  23. Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation

    Time frame: from baseline to 14 days after treatment initiation

    beta rhythm index (%) assessed by electroencephalogram

  24. Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion

    Time frame: from baseline to 90±7 days after inclusion

    alpha rhythm index (%) assessed by electroencephalogram

  25. Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion

    Time frame: from baseline to 90±7 days after inclusion

    beta rhythm index (%) assessed by electroencephalogram

  26. Number of participants with treatment-related adverse events assessed according to the protocol-specified adverse effects

    Time frame: 14 days after treatment initiation

    Number of participants with treatment-related adverse events assessed according to the Toronto Side Effects Scale

Study contacts

Contact information is provided by the study sponsor or research team.

Lyudmila Korostovtseva

CONTACT

[email protected]

+79217873548

Sponsors and collaborators

Lead sponsor

Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Other

Registry information

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Feb 18, 2022
Registry last updated
Aug 8, 2025

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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