Ischemic Stroke, Acute Clinical Trial
Official title:
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.
| Status | Recruiting |
| Enrollment | 80 |
| Est. completion date | July 31, 2024 |
| Est. primary completion date | May 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Russian Federation | Almazov National Medical Research Centre | St Petersburg |
| Lead Sponsor | Collaborator |
|---|---|
| Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health |
Russian Federation,
Bochkarev MV, Korostovtseva LS, Medvedeva EA, Rotar OP, Sviryaev YV, Zhernakova YV, Shalnova SA, Konradi AO, Chazova IE, Boitsov SA, Shlyakhto EV. [Sleep disorders and stroke: data of the esse-rf study]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(4. Vyp. 2):73-80. doi: 10.17116/jnevro201911904273. Russian. — View Citation
Korostovtseva L. Ischemic Stroke and Sleep: The Linking Genetic Factors. Cardiol Ther. 2021 Dec;10(2):349-375. doi: 10.1007/s40119-021-00231-9. Epub 2021 Jun 30. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Change from baseline in time in bed assessed by actigraphy | time in bed (minutes) | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in total sleep time assessed by actigraphy | total sleep time (minutes) | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in sleep efficiency assessed by actigraphy | sleep efficiency (%) | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in sleep onset latency assessed by actigraphy | sleep onset latency (min) | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in number of awakenings assessed by actigraphy | number of awakenings | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in mean motor activity assessed by actigraphy | mean motor activity (units) | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in Sleep Quality Score assessed by questionnaire Pittsburgh Sleep Quality Index | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in daytime sleepiness assessed by Epworth Sleepiness Scale | Epworth Sleepiness Scale is a common tool to assess sleepiness; 0-24 points, higher score indicate greater sleepiness | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in fatigue severity assessed by Fatigue severity Scale | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in Insomnia severity index | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in sensorimotor assessment of upper limbs | Sensorimotor assessment of upper limbs by Fugl-Meyer is a stroke-specific, performance-based impairment index. The total possible scale score is 226 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in melatonin curve secretion | salivary melatonin levels samples collected every 3 hours for 24 hours at study inclusion and at 14 days after study inclusion | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in cortisol curve secretion | salivary cortisol sampled every 3 hours for 24 hours at study inclusion and at 14 days after study inclusion | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in circadian brain-derived neurotrophic factor messenger ribonucleic acid (mRNA) expression | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in circadian clock gene CLOCK messenger ribonucleic acid (mRNA) expression | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in circadian clock gene Bmal1 messenger ribonucleic acid (mRNA) expression | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change from baseline in circadian Melatonin receptor messenger ribonucleic acid (mRNA) expression | 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 | from baseline to 14 days after treatment initiation | |
| Other | Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 14 days | heart rate variability assessed by electrocardiogram (maximum heart rate - minimum heart rate, beats per minute) | from baseline to 14 days after treatment initiation | |
| Other | Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 90 days after inclusion | heart rate variability assessed by electrocardiogram (maximum heart rate - minimum heart rate, beats per minute) | from baseline to 90±7 days after inclusion | |
| Other | Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method - from baseline to 14 days | respiratory movement amplitude assessed by respiratory rate abdominal and thoracic sensors (units) | from baseline to 90±7 days after treatment initiation | |
| Other | Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method- from baseline to 90 days | respiratory movement amplitude assessed by respiratory rate abdominal and thoracic sensors (units) | from baseline to 90±7 days after inclusion | |
| Other | Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation | alpha rhythm index (%) assessed by electroencephalogram | from baseline to 14 days after treatment initiation | |
| Other | Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation | beta rhythm index (%) assessed by electroencephalogram | from baseline to 14 days after treatment initiation | |
| Other | Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion | alpha rhythm index (%) assessed by electroencephalogram | from baseline to 90±7 days after inclusion | |
| Other | Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion | beta rhythm index (%) assessed by electroencephalogram | from baseline to 90±7 days after inclusion | |
| Other | Number of participants with treatment-related adverse events assessed according to the protocol-specified adverse effects | Number of participants with treatment-related adverse events assessed according to the Toronto Side Effects Scale | 14 days after treatment initiation | |
| Primary | Change in the value of National Institutes of Health Stroke Scale from baseline to 14 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 | From baseline to 14 days after treatment initiation | |
| Primary | Stroke-related disability assessed by the change in modified Rankin scale 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) | From baseline to 14 days after treatment initiation | |
| Primary | Stroke-related disability assessed by the change in Rivermead Mobility Index 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) | From baseline to 14 days after treatment initiation | |
| Primary | Stroke-related disability assessed by the change in Barthel Index 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) | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Psychomotor vigilance task (mean reaction time) 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 | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Psychomotor vigilance task (mean reaction time) from baseline to 90 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 | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Kraepelin test 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) | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Kraepelin test from baseline to 90 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) | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Trail Making test 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 | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Trail Making test from baseline to 90 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) | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Victoria Stroop test 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) | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Victoria Stroop test from baseline to 90 days 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) | From baseline to 90±7 day after inclusion | |
| Secondary | Change in Hopkins Verbal Learning Test (Revised) 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. | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Hopkins Verbal Learning Test (Revised) from baseline to 90 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. | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Brief Visuospatial Memory Test (Revised) 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. | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Brief Visuospatial Memory Test (Revised) from baseline to 90 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. | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Wechsler Memory Scale (Revised) 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. | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Wechsler Memory Scale (Revised) from baseline to 90 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. | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Corsi block-tapping test 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. | From baseline to 14 days after treatment initiation | |
| Secondary | Change in Corsi block-tapping test from baseline to 90 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. | From baseline to 90±7 days after inclusion | |
| Secondary | Change from baseline in objective sleep duration assessed by polysomnography | Sleep duration (minutes) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in objective sleep efficiency assessed by polysomnography | sleep efficiency (%) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in objective sleep latency assessed by polysomnography | sleep latency (minutes) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in sleep S1 stage duration assessed by polysomnography | S1 sleep stage percentage of total sleep time (%) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in sleep S2 stage duration assessed by polysomnography | S2 sleep stage percentage of total sleep time (%) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in sleep S3 stage duration assessed by polysomnography | S3 sleep stage percentage of total sleep time (%) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in rapid eye movement (REM) sleep stage duration assessed by polysomnography | Rapid eye movement (REM) sleep stage percentage of total sleep time (%) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in wake-after-sleep-onset time assessed by polysomnography | wake after sleep onset time (minutes) | From baseline to 14 days after treatment initiation | |
| Secondary | Change from baseline in arousal index assessed by polysomnography | Arousal index (episodes/hour of sleep) | From baseline to 14 days after treatment initiation | |
| Secondary | Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 90 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 | from baseline to 14 days after treatment initiation | |
| Secondary | Change in emotional outcome assessed by Hospital anxiety and depression scale 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 | From baseline to 90±7 days after inclusion | |
| Secondary | Assessment of mood by change in Visual Analogue Mood Scale 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 | from baseline to 14 days after treatment initiation | |
| Secondary | Assessment of mood by change in Visual Analogue Mood Scale from baseline to 90 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 | From baseline to 90±7 days after inclusion | |
| Secondary | Change in the value of National Institutes of Health Stroke Scale from baseline to 90 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 | From baseline to 90±7 days after inclusion | |
| Secondary | Change in modified Rankin scale from baseline to 90 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) | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Rivermead Mobility Index from baseline to 90 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) | From baseline to 90±7 days after inclusion | |
| Secondary | Change in Barthel Index from baseline to 90 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) | From baseline to 90±7 days after inclusion |