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

Обзор

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.

Подробное описание

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).

Вмешательства

• Комбинированный продукт Blue light exposure + Melatonin treatment
  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.
• Препарат Melatonin treatment
  3 mg Melatonin pill will be given 1 hour before going to bed.
• Устройство Blue light exposure
  Blue light exposure will be performed during 30-minute sessions with the use of the lamps (Lumie/Vitamin L) in the morning.
• Комбинированный продукт Placebo
  Placebo light exposure will be performed by using lamp turned off; and placebo pill will be given in the evening

Первичные конечные точки

• Change in the value of National Institutes of Health Stroke Scale from baseline to 14 days after inclusion [Срок оценки: From baseline to 14 days after treatment initiation]
• Stroke-related disability assessed by the change in modified Rankin scale from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Stroke-related disability assessed by the change in Barthel Index from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]

Вторичные конечные точки (12)

• Change in Psychomotor vigilance task (mean reaction time) from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Psychomotor vigilance task (mean reaction time) from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 days after inclusion]
• Change in Kraepelin test from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Kraepelin test from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 days after inclusion]
• Change in Trail Making test from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Trail Making test from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 days after inclusion]
• Change in Victoria Stroop test from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Victoria Stroop test from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 day after inclusion]
• Change in Hopkins Verbal Learning Test (Revised) from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Hopkins Verbal Learning Test (Revised) from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 days after inclusion]
• Change in Brief Visuospatial Memory Test (Revised) from baseline to 14 days after treatment initiation [Срок оценки: From baseline to 14 days after treatment initiation]
• Change in Brief Visuospatial Memory Test (Revised) from baseline to 90 days after inclusion [Срок оценки: From baseline to 90±7 days after inclusion]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• Almazov National Medical Research Centre — Saint Petersburg

Публикации

• 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. PMID 34191267
• 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. PMID 31317919

Идентификаторы

NCT: NCT05247125 · 21-75-10173-1 (interventional)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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