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

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

Status and phase: Enrolling; Phase 4

Conditions: Ischemic Stroke, Acute; Sleep Disorders, Circadian Rhythm

Treatments: Drug: Melatonin treatment; Combination Product: Blue light exposure + Melatonin treatment; Combination Product: Placebo; Device: Blue light exposure

Study type: Interventional

Funder types: Other

Identifiers

NCT05247125

21-75-10173-1 (interventional)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 4 patient groups, including a placebo group

Blue light exposure + Melatonin treatment

Experimental group

Description:

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

Treatment:

Combination Product: Blue light exposure + Melatonin treatment

Melatonin treatment

Experimental group

Description:

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

Treatment:

Drug: Melatonin treatment

Blue light exposure

Experimental group

Description:

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)

Treatment:

Device: Blue light exposure

Placebo group

Placebo Comparator group

Description:

The participants will receive placebo light exposure in the morning (lamp turned off) and placebo pill treatment in the evening for 14 days

Treatment:

Combination Product: Placebo