The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14 days after treatment initiation
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Blue light exposure + Melatonin treatment
The participants will receive the combination of blue light exposure according to the protocol described by Killgore et al. (2020) and 3 mg of melatonin 1 hour before going to sleep (approximately at 20:00) (Ramos et al 2020) for 14 days
干预措施: Blue light exposure + Melatonin treatment (Combination Product)
Melatonin treatment
The participants will receive 3 mg of melatonin 1 hour before going to sleep (approximately at 20:00) (Ramos et al 2020) and the morning placebo-light exposure according to the protocol described by Killgore et al. (2020) for 14 days
干预措施: Melatonin treatment (Drug)
Blue light exposure
The participants will receive the morning blue light exposure according to the protocol described by Killgore et al. (2020) for 14 days and placebo pill 1 hour before going to sleep (approximately at 20:00)
干预措施: Blue light exposure (Device)
Placebo group
The participants will receive placebo light exposure in the morning (lamp turned off) and placebo pill treatment in the evening for 14 days
干预措施: Placebo (Combination Product)
结局指标
主要结局
Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14 days after treatment initiation
时间窗: 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)
Stroke-related disability assessed by the change in Barthel Index from baseline to 14 days after treatment initiation
时间窗: 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)
Stroke-related disability assessed by the change in modified Rankin scale from baseline to 14 days after treatment initiation
时间窗: 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)
Change in the value of National Institutes of Health Stroke Scale from baseline to 14 days after inclusion
时间窗: 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
次要结局
- Change in Kraepelin test from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Victoria Stroop test from baseline to 90 days after inclusion(From baseline to 90±7 day after inclusion)
- Change in Psychomotor vigilance task (mean reaction time) from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Brief Visuospatial Memory Test (Revised) from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Hopkins Verbal Learning Test (Revised) from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Brief Visuospatial Memory Test (Revised) from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Wechsler Memory Scale (Revised) from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change from baseline in sleep S2 stage duration assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change in Psychomotor vigilance task (mean reaction time) from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Kraepelin test from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Trail Making test from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Trail Making test from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Victoria Stroop test from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change in Hopkins Verbal Learning Test (Revised) from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Wechsler Memory Scale (Revised) from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change from baseline in sleep S3 stage duration assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change from baseline in rapid eye movement (REM) sleep stage duration assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 90 days after inclusion(from baseline to 14 days after treatment initiation)
- Change in Corsi block-tapping test from baseline to 14 days after treatment initiation(From baseline to 14 days after treatment initiation)
- Change from baseline in objective sleep duration assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change from baseline in objective sleep efficiency assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change from baseline in arousal index assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Assessment of mood by change in Visual Analogue Mood Scale from baseline to 14 days after treatment initiation(from baseline to 14 days after treatment initiation)
- Change in Corsi block-tapping test from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change from baseline in objective sleep latency assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change from baseline in sleep S1 stage duration assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 14 days after treatment initiation(From baseline to 90±7 days after inclusion)
- Assessment of mood by change in Visual Analogue Mood Scale from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Rivermead Mobility Index from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in Barthel Index from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change from baseline in wake-after-sleep-onset time assessed by polysomnography(From baseline to 14 days after treatment initiation)
- Change in the value of National Institutes of Health Stroke Scale from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
- Change in modified Rankin scale from baseline to 90 days after inclusion(From baseline to 90±7 days after inclusion)
研究者
Lyudmila Korostovtseva
Senior Researcher, Department for Hypertension
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health