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

The study is aimed at the investigation of the association of biomarkers of circadian rhythms with sleep characteristics and stroke outcome in acute stroke patients. It is designed as an observational cohort study with the retrospective and prospective longitudinal arms.

Study Overview

• Status: Recruiting
• Conditions: Sleep Disorder; Stroke, Ischemic
• Intervention / Treatment: Other: No intervention is planned

Detailed Description

In the retrospective arm of the study, the routinely collected data of patients admitted to the stroke unit with acute ischemic stroke (from 2018 till 2022) will be evaluated. In the prospective longitudinal arm, about 200-250 patients admitted to the Stroke Unit of one participating center will undergo examination including the assessment of medical records, stroke characteristics, sleep characteristics and blood sampling for the evaluation of genetic biomarkers of circadian rhythms within the first 2-3 days after admission.The assessment of stroke severity and functional deficit will be repeated at 10-14 days after stroke.

The following associations will be assessed:

• the association of genetic biomarkers of circadian rhythms with stroke outcome (the difference in neurological and functional deficit from admission to 14th day after stroke), with stroke characteristics (stroke subtype and neuroimaging stroke parameters) and with sleep characteristics.
• the association of sleep characteristics with stroke outcome (the difference in neurological and functional deficit from admission to 14th day after stroke) and with stroke characteristics (stroke subtype and neuroimaging stroke parameters).

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Lyudmila Korostovtseva, MD, PHD; Phone Number: +79217873548; Email: lyudmila_korosto@mail.ru

Study Locations

• Russian Federation
  • St Petersburg, Russian Federation, 197341
    • Recruiting
    • Almazov National Medical Research Centre
    • Contact: Lyudmila Korostovtseva; Phone Number: 89217873548; Email: lyudmila_korosto@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the patients with confirmed acute ischemic stroke admitted to the Stroke Unit

Description

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 -2)
• clinically unstable or life-threatening conditions
• known progressive neurological diseases
• known psychiatric diseases
• concomitant benzodiazepine medication
• drug or alcohol abuse
• pregnancy
• disability to participate in the study
• congestive heart failure with reduced ejection fraction (<=45%) or New York Heart Association (NYHA) classification III-IV functional class

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective cohort; Patients with acute ischemic stroke admitted to the Stroke Unit of one participating center in 2018-2022. The data collected within clinical routine will be analyzed including stroke characteristics at baseline and at discharge (10-14 days after admission), neuroimaging data, sleep characteristics (routine polygraphy study), heart rate variability, routine blood tests.	Other: No intervention is planned; No intervention is planned
Prospective cohort; Approximately 200-250 patients with acute ischemic stroke admitted to the Stroke Unit of one participating center in 2022-2024 will undergo the assessment of medical records, stroke characteristics, the assessment of sleep characteristics and blood sampling for the evaluation of genetic biomarkers of circadian rhythms at baseline (within 2-3 days of admission) and at 10-14 days (at discharge).	Other: No intervention is planned; No intervention is planned

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the value of National Institutes of Health Stroke Scale from baseline to 14th day 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 14th day after treatment initiation
Stroke-related disability assessed by the change in modified Rankin scale from baseline to 14th day 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 14th day after treatment initiation
Stroke-related disability assessed by the change in Rivermead Mobility Index from baseline to 14th day after treatment initiation	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 14th day after treatment initiation
Stroke-related disability assessed by the change in Barthel Index from baseline to 14th day after treatment initiation	a common scale used to measure performance in activities of daily living, 0-100 scores, higher scores define better performance	From baseline to 14th day after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality assessed by Pittsburgh Sleep Quality Index	Pittsburgh Sleep Quality Index is a self-rated questionnaire which assesses sleep quality and disturbances over the last (previous) 1-month (a retrospective assessment) 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	Baseline
Sleepiness assessed by Epworth Sleepiness Scale	a common tool to assess sleepiness; 0-24 points, higher score indicate greater sleepiness	Baseline
Fatigue assessed by Fatigue severity Scale	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	Baseline
Insomnia assessed by Insomnia severity index	a 7-item tool to assess the severity of insomnia, 0-5 points per each item, higher score indicates more severe insomnia	Baseline
Chronotype assessed by Morningness-Eveningness Questionnaire	a common 19-item tool to estimate individual chronotype, a score ranging from 16 to 86; scores of 41 and below indicate "evening types", scores of 59 and above indicate "morning types", scores between 42-58 indicate "intermediate types"	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
sleep-related respiratory characteristics: apnea-hypopnea index	assessed by routine polygraphy: apnea-hypopnea index (higher values indicate greater severity; <5 episodes/h - normal, >=5 episodes/h - pathological)	Baseline
sleep-related respiratory characteristics: oxygen desaturation index	assessed by routine polygraphy: oxygen desaturation index (higher values indicate greater severity; <5 episodes/h - normal, >=5 episodes/h - pathological)	Baseline
sleep-related respiratory characteristics: time under oxygen saturation <90%	assessed by routine polygraphy: time under oxygen saturation <90% (higher values indicate greater severity), in minutes	Baseline
sleep-related respiratory characteristics: average oxygen saturation	assessed by routine polygraphy: average oxygen saturation (lower values indicate greater severity), in %	Baseline
sleep-related respiratory characteristics: lowest oxygen saturation	assessed by routine polygraphy: lowes oxygen saturation (lower values indicate greater severity), in %	Baseline
Nocturnal heart rate variability characteristics derived from nocturnal pulseoximeter data: standard deviation of normal-to-normal intervals	standard deviation of normal-to-normal intervals (msec)	Baseline
Nocturnal heart rate variability characteristics derived from nocturnal pulseoximeter data: number of interval differences of successive heart beats greater than 50 ms	number of interval differences of successive heart beats greater than 50 ms	Baseline
Nocturnal heart rate variability characteristics derived from nocturnal pulseoximeter data: spectral power in high-frequency power bands	spectral power in high-frequency power bands (Hz)	Baseline
Nocturnal heart rate variability characteristics derived from nocturnal pulseoximeter data: spectral power in low-frequency power bands	spectral power in low-frequency power bands (Hz)	Baseline
Sleep duration assessed by polysomnography	Sleep duration (minutes)	Baseline
Sleep efficiency assessed by polysomnography	sleep efficiency (%)	Baseline
Sleep latency assessed by polysomnography	sleep latency (minutes)	Baseline
Sleep S1 stage duration assessed by polysomnography	S1 sleep stage percentage of total sleep time (%)	Baseline
Sleep S2 stage duration assessed by polysomnography	S2 sleep stage percentage of total sleep time (%)	Baseline
Sleep S3 stage duration assessed by polysomnography	S3 sleep stage percentage of total sleep time (%)	Baseline
Rapid eye movement (REM) stage duration assessed by polysomnography	Rapid eye movement (REM) sleep stage percentage of total sleep time (%)	Baseline
Wake after sleep onset time assessed by polysomnography	wake after sleep onset time (minutes), higher values indicate worse disturbance	Baseline
Arousal index assessed by polysomnography	Arousal index (episodes/hour of sleep), higher values indicate worse disturbance	Baseline
periodic limb movement index assessed by polysomnography	periodic limb movement index (episodes/hour of sleep), higher values indicate worse disturbance	Baseline
Stroke lesion volume	Stroke lesion volume assessed by neuroimaging (computer tomography scan or magnetic resonance imaging) (ml or mm3)	Baseline

Collaborators and Investigators

• Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Investigators: Principal Investigator: Lyudmila Korostovtseva, MD, PhD, Almazov National Medical Research Centre

Publications and helpful links

General Publications

• 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.
• Seiler A, Camilo M, Korostovtseva L, Haynes AG, Brill AK, Horvath T, Egger M, Bassetti CL. Prevalence of sleep-disordered breathing after stroke and TIA: A meta-analysis. Neurology. 2019 Feb 12;92(7):e648-e654. doi: 10.1212/WNL.0000000000006904. Epub 2019 Jan 11.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: February 5, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: neuroplasticity; disability; circadian rhythm; heart rate variability; cognitive dysfunction; functional deficit; stroke outcome; sleep-disordered breathing
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia; Sleep Wake Disorders
• Other Study ID Numbers: 21-75-1017-2 (observational)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No