Epigenome-wide DNA Methylation Profiling in Aneurysmal Subarachnoid Hemorrhage and Delayed Ischemic Neurologic Deficit

NCT06881329 | Active Not Recruiting

• 2 other identifiers: KB-0012/61/20212021/41/N/NZ2/00844
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to investigate DNA methylation changes in adults with bleeding from brain aneurysm, which is called aneurysmal subarachnoid hemorrhage (aSAH), and their association with delayed ischemic neurologic deficit (DIND). The main questions it aims to answer are: Are there specific DNA methylation changes in peripheral blood that differentiate patients with aSAH from healthy individuals? Can DNA methylation changes in peripheral blood predict the development of DIND following aSAH? Researchers will compare blood DNA methylation profiles of aSAH patients to healthy controls and also do subgroup analysis of patients with DIND versus those without DIND to see if there are distinct methylation patterns associated with aSAH and DIND. Participants with aSAH will:

• Have a blood sample collected shortly after admission to hospital.
• Undergo epigenome-wide DNA methylation profiling using the Infinium MethylationEPIC v2.0 BeadChip microarray.
• Be monitored for the development of DIND, defined by clinical symptoms and radiographic vasospasm. This study aims to identify potential epigenetic biomarkers for aSAH susceptibility and DIND risk, which could improve early diagnosis and risk stratification in affected patients.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Delayed Cerebral Ischemia; Cerebral Vasospasm After Subarachnoid Hemorrhage; Intracranial Aneurysm

Keywords

aneurysmal subarachnoid hemorrhage; cerebral vasospasm; delayed ischemic neurologic deficit; delayed cerebral ischemia; aneurysm rupture; intracranial aneurysm

Outcome Measures

Primary Outcomes (1)

• DNA methylation changes associated with aneurysmal subarachnoid hemorrhage and delayed ischemic neurologic deficit

  Identification of differentially methylated CpG sites in peripheral blood DNA of patients with aneurysmal subarachnoid hemorrhage compared to healthy controls and to assess whether DNA methylation changes are associated with delayed ischemic neurologic deficit. The metrics and direction of DNA methylation changes will be reported as Δβ values

  Within four days following the enrollment (as blood samples will be collected within days 1-4 post-hemorrhage). Methylation profiling and CpG analysis the entire batch will be conducted within one year following enrollment of the last participant

Secondary Outcomes (1)

• Epigenetic clocks analysis and their association with chronological age in delayed ischemic neurologic deficit

  Within four days following the enrollment (as blood samples will be collected within days 1-4 post-hemorrhage). Methylation profiling and epigenetic clock analysis will be conducted within one year following enrollment of the last participant

Study Arms (3)

Subarachnoid hemorrhage with delayed ischemic neurologic deficit

This cohort includes patients diagnosed with aneurysmal subarachnoid hemorrhage who develop delayed ischemic neurologic deficit, defined as a new focal neurological deficit (paresis, dysphasia) or Glasgow Coma Scale decline of ≥2 points lasting \>1 hour, not attributable to rebleeding, hydrocephalus, or hyponatremia. Diagnosis is confirmed with radiologic evidence of vasospasm on transcranial Doppler.

Subarachnoid hemorrhage without delayed ischemic neurologic deficit

This cohort includes patients diagnosed with aneurysmal subarachnoid hemorrhage who do not develop delayed ischemic neurologic deficit. These patients exhibit no new focal neurological deficits and no Glasgow Coma Scale decline of ≥2 points beyond the acute phase of hemorrhage. Radiologic assessments confirm the absence of significant vasospasm on transcranial Doppler.

Healthy controls without subarachnoid hemorrhage

This cohort consists of age-, sex-, race-, and ethnicity-matched healthy individuals with no history of aneurysmal subarachnoid hemorrhage (aSAH) or other neurological disorders. Participants were selected from a publicly available dataset (GSE246337). Blood DNA methylation profiles from this group serve as a baseline reference for comparison with aSAH patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from a tertiary neurosurgical center at Pomeranian Medical University Hospital No. 1 in Szczecin, Poland. The study population includes consecutive adult patients diagnosed with aneurysmal subarachnoid hemorrhage who meet eligibility criteria. Patients are prospectively enrolled upon admission and followed for the development of delayed ischemic neurologic deficit. The control group consists of age-, sex-, race-, and ethnicity-matched healthy individuals selected from the publicly available GSE246337 dataset. This dataset serves as a reference population to identify epigenetic changes specific to aSAH.

You may qualify if:

• subarachnoid hemorrhage in computed tomography (CT) scan
• ruptured aneurysm identified with angio-CT or digital subtraction angiography (DSA)
• aneurysm successfully embolized or clipped
• obtained informed consent
• Hunt-Hess grade ≤ 3 by day 14 (initial higher grade was allowed providing that patient improved to grade 3 or higher by day 14)

You may not qualify if:

• \< 18 years old
• unable to sign informed consent
• diagnosis of idiopathic perimesencephalic subarachnoid hemorrhage
• aneurysm identified more than 14 days after the ictus
• more than 14 days at the Intensive Care Unit
• remaining in Hunt Hess grade 5 or World Federation of Neurological Surgeons (WFNS) grade 5 from admission up to post-bleeding day 14

Sponsors & Collaborators

• Pomeranian Medical University Szczecin: lead
• National Science Centre, Poland: collaborator

Study Sites (1)

Pomeranian Medical University Hospital No. 1

Szczecin, West Pomeranian Voivodeship, 71-252, Poland

Location

Related Publications (1)

• Klepinowski T, Przybylowicz P, Taryma-Lesniak O, Binkowski J, Lisman D, Ossowski A, Jarosz K, Sawicki M, Poncyljusz W, Taterra D, Latka K, Wojdacz TK, Sagan L. Epigenome-wide DNA methylation profiling in aneurysmal subarachnoid hemorrhage and delayed ischemic neurologic deficit: a prospective observational study. Int J Surg. 2025 Sep 4. doi: 10.1097/JS9.0000000000003324. Online ahead of print.

  PMID: 40905839 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral venous whole blood samples

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Intracranial Aneurysm; Vasospasm, Intracranial; Aneurysm, Ruptured

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arterial Diseases; Aneurysm

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Researcher at the Department of Neurosurgery

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 18, 2025
• Study Start: December 20, 2021
• Primary Completion: January 12, 2025
• Study Completion: December 31, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data is already deposited in Gene Expression Omnibus repository (GSE290201) and will be available immediately upon publication. It will remain publicly accessible indefinitely according to GEO repository policies.
• Access Criteria: The methylation dataset will be available for download from Gene Expression Omnibus (GEO) repository (GSE290201). Researchers will have an access to the data following GEO's standard data use agreements, which require appropriate citation of the original study.

Locations

PL (1)