Transcriptomic Signature of Vasospasm Consecutive to Sub-arachnoid Aneurismal Hemorrhage

Discovery of the Risk Factors Associated to the Development of Vasospasm Following a Sub-arachnoid Aneurismal Hemorrhage Via Genomic Studies Including Genetic and Transcriptomic

Rational: The main danger with intracranial aneurism is its rupture conjugated with subarachnoid hemorrhage (SAH) occurrence. SAH is a severe pathology leading not only to neurological but also extra cerebral disorders. The major cause of morbidity and mortality when developing a SAH is the secondary development of a delayed cerebral ischemia consecutive to a prolonged vasospasm of cerebral arteries. The understanding of the pathophysiological mechanisms of SAH complication, such as vasospasm which is the more frequent, is essential.

Vasospasm is defined as a reversible shrinking of an artery lumen diameter in the subarachnoid space, beginning generally between 4 and 12 days after the hemorrhage. Such a vasospasm could have a huge clinical impact leading to delayed neurological ischemic deficiency in 17 to 40 % of cases. Up to day, mechanisms involved in vasospasm occurrence are not well described.

Disposing of well-established genetics and transcriptomics databases along with cerebral ischemia and inflammation is essential to unravel the mechanisms leading to vasospasm occurrence on SAH patients. It will enable researchers to better comprehend SAH pathology and elaborate an efficient and individualized therapeutic strategy to SAH acute phase in order to reduce the risk of vasospasm occurrence.

Aims: 1) Constitute DNA and RNA Biobank via blood proofing oh SAH patients 2) Constitute a database grouping clinical and biological data 3) Look for genetic and transcriptomic early markers via genomic approaches 4) Correlate these different markers with vasospasm occurrence and clinical evolution of the patients

Study: Patients inclusion will be done following their admission (D1) in the " unité de réanimation neurochirurgicale" of Pitié-Salpètrière Hospital. After obtaining of the informed consent, blood proofing will be realized daily during 12 days: one daily 2.5ml tube for the transcriptomic study and a single 10ml EDTA tube for genetic analyses. Clinical and biological follow-up will be performed as usual.

200 patients will be initially included during 2 to 3 years for the transcriptomic study of which 1/3 will develop vasospastic complication. The transcriptomic study will thus be performed by comparing patients developing or not developing this complication

Expected Results: Unravel vasospasm early genetic markers.

Study Overview

• Status: Completed
• Conditions: Aneurysmal Subarachnoid Hemorrhage; Vasospasm
• Intervention / Treatment: Genetic: Case-control transcriptomic study

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Neuro-anesthesia intensive care unit, Pitié-Salpétrière hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Caucasian subjects, aged more than 18, suffering of sub-arachnoid hemorrhage

Description

Inclusion Criteria:

• Patient entering the neurosurgical unit in the 48 hours following an aneurismal sub-arachnoid hemorrhage and treated in the 96 first hours (embolization or surgery)
• Aged more than 18
• Caucasian origin
• Affiliated to a social care service
• Having (or one of is related if he is comatose) given its informed consent

Exclusion Criteria:

• Subjects which do not have a social care protection
• Subjects (or one of is related if he is comatose) refusing to sign the consent
• Subjects being under a protective juridical system for adults

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vasospastic patients; Any patient send to the neuro-anesthesia intensive care unit in the 48 hours following an aneurismal sub-arachnoid hemorrhage and treated in the 96 first hours (embolization or surgery) and developing a vasospasm during the first 12 days after the bleeding; aged more than 18; of Caucasian origin; affiliated to a social care service; having (or one of is related if he is comatose) given its informed consent	Genetic: Case-control transcriptomic study; No intervention
Control patients; Any patient send to the neuro-anesthesia intensive care unit in the 48 hours following an aneurismal sub-arachnoid hemorrhage and treated in the 96 first hours (embolization or surgery) not developing a vasospasm during the first 12 days after the bleeding; aged more than 18; of Caucasian origin; affiliated to a social care service; having (or one of is related if he is comatose) given its informed consent	Genetic: Case-control transcriptomic study; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of clinically definite vasospasm	Any cases will be reviewed by an expert committee to establish vasospasm diagnosis Diagnosis criteria: Cerebral angiography,; Trans-cranial Doppler of the MCA at 120 cm/s or two days of changing in the mean speed of the MCA at trans-cranial Doppler superior to 50 cm/s.; Development of new clinical symptoms for conscious patients	Between intensive care unit admission and day twelve

Secondary Outcome Measures

Outcome Measure	Time Frame
Rankin Score	6 months and 1 year after ICU discharge
Glasgow outcome score (GOS)	6 months and 1 year after ICU discharge

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Director: Sophie Garnier, Lecturer, INSERM and University Pierre and Marie Curie; Study Chair: Louis Puybasset, MD PhD, Pierre and Marie Curie University

Publications and helpful links

General Publications

• Pulcrano-Nicolas AS, Proust C, Clarencon F, Jacquens A, Perret C, Roux M, Shotar E, Thibord F, Puybasset L, Garnier S, Degos V, Tregouet DA. Whole-Blood miRNA Sequencing Profiling for Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage. Stroke. 2018 Sep;49(9):2220-2223. doi: 10.1161/STROKEAHA.118.021101.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 4, 2016

Study Registration Dates

• First Submitted: January 10, 2013
• First Submitted That Met QC Criteria: January 28, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Actual): August 30, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Vasospasm; Case-Control Study; Aneurysmal subarachnoid hemorrhage; Transcriptomic
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: C10-15; 2012-A00935-38 (Registry Identifier: IDRCB)