Clinical trial NCT05247125: The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)
Official title: The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ischemic Stroke, Acute
Sleep Disorders, Circadian Rhythm
Keywords: circadian misalignment
neuroplasticity
melatonin
light therapy
circadian disorder
Lead sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Sponsor class: OTHER
First posted: 2022-02-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients will be randomized into 4 parallel groups
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the value of National Institutes of Health Stroke Scale from baseline to 14 days after inclusion
timeFrame: From baseline to 14 days after treatment initiation
measure: Stroke-related disability assessed by the change in modified Rankin scale from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Stroke-related disability assessed by the change in Barthel Index from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
Secondary outcomes:
measure: Change in Psychomotor vigilance task (mean reaction time) from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Psychomotor vigilance task (mean reaction time) from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Kraepelin test from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Kraepelin test from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Trail Making test from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Trail Making test from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Victoria Stroop test from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Victoria Stroop test from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 day after inclusion
measure: Change in Hopkins Verbal Learning Test (Revised) from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Hopkins Verbal Learning Test (Revised) from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Brief Visuospatial Memory Test (Revised) from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Brief Visuospatial Memory Test (Revised) from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Wechsler Memory Scale (Revised) from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Wechsler Memory Scale (Revised) from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Corsi block-tapping test from baseline to 14 days after treatment initiation
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in Corsi block-tapping test from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change from baseline in objective sleep duration assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in objective sleep efficiency assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in objective sleep latency assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in sleep S1 stage duration assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in sleep S2 stage duration assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in sleep S3 stage duration assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in rapid eye movement (REM) sleep stage duration assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in wake-after-sleep-onset time assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change from baseline in arousal index assessed by polysomnography
timeFrame: From baseline to 14 days after treatment initiation
measure: Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 90 days after inclusion
timeFrame: from baseline to 14 days after treatment initiation
measure: Change in emotional outcome assessed by Hospital anxiety and depression scale from baseline to 14 days after treatment initiation
timeFrame: From baseline to 90±7 days after inclusion
measure: Assessment of mood by change in Visual Analogue Mood Scale from baseline to 14 days after treatment initiation
timeFrame: from baseline to 14 days after treatment initiation
measure: Assessment of mood by change in Visual Analogue Mood Scale from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in the value of National Institutes of Health Stroke Scale from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in modified Rankin scale from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Rivermead Mobility Index from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
measure: Change in Barthel Index from baseline to 90 days after inclusion
timeFrame: From baseline to 90±7 days after inclusion
Other outcomes:
measure: Change from baseline in time in bed assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in total sleep time assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in sleep efficiency assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in sleep onset latency assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in number of awakenings assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in mean motor activity assessed by actigraphy
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in Sleep Quality Score assessed by questionnaire Pittsburgh Sleep Quality Index
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in daytime sleepiness assessed by Epworth Sleepiness Scale
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in fatigue severity assessed by Fatigue severity Scale
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in Insomnia severity index
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in sensorimotor assessment of upper limbs
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in melatonin curve secretion
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in cortisol curve secretion
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in circadian brain-derived neurotrophic factor messenger ribonucleic acid (mRNA) expression
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in circadian clock gene CLOCK messenger ribonucleic acid (mRNA) expression
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in circadian clock gene Bmal1 messenger ribonucleic acid (mRNA) expression
timeFrame: from baseline to 14 days after treatment initiation
measure: Change from baseline in circadian Melatonin receptor messenger ribonucleic acid (mRNA) expression
timeFrame: from baseline to 14 days after treatment initiation
measure: Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 14 days
timeFrame: from baseline to 14 days after treatment initiation
measure: Change in psychophysiological state: heart rate variability assessed by biofeedback method from baseline to 90 days after inclusion
timeFrame: from baseline to 90±7 days after inclusion
measure: Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method - from baseline to 14 days
timeFrame: from baseline to 90±7 days after treatment initiation
measure: Change in psychophysiological state: respiratory movement amplitude assessed by biofeedback method- from baseline to 90 days
timeFrame: from baseline to 90±7 days after inclusion
measure: Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation
timeFrame: from baseline to 14 days after treatment initiation
measure: Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 14 days after treatment initiation
timeFrame: from baseline to 14 days after treatment initiation
measure: Change in psychophysiological state: alpha-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion
timeFrame: from baseline to 90±7 days after inclusion
measure: Change in psychophysiological state: beta-rhythm index assessed by biofeedback method - from baseline to 90 days after inclusion
timeFrame: from baseline to 90±7 days after inclusion
measure: Number of participants with treatment-related adverse events assessed according to the protocol-specified adverse effects
timeFrame: 14 days after treatment initiation
Locations:
city: St Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
Study officials:
affiliation: Almazov National Medical Research Centre
name: Lyudmila Korostovtseva
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.