Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study

Phase 4

Completed

• Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm
• Interventions: Drug: Eicosapentaenoic acid ethyl ester

• Registration Number: NCT00839449
• Lead Sponsor: Yamaguchi University Hospital

Brief Summary

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most common cause of morbidity and mortality. Recent studies indicate that Rho-kinase play an important role in the occurrence of such cerebral vasospasm. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine (SPC)-induced Rho-kinase activation in vitro. So this study examines whether EPA prevents cerebral vasospasm occurrence after SAH in patients.

Detailed Description

Cerebral vasospasm occasionally seen after subarachnoid hemorrhage (SAH) due to a ruptured intracranial aneurysm is the most common cause of morbidity and mortality in these cases. Recent studies indicate that Rho-kinase plays an important role in such cerebral vasospasm and that numerous agents, such as thromboxane A2 (TXA2), sphingosylphosphorylcholine (SPC) and arachidonic acid (AA), can activate Rho-kinase directly or through receptors in the cell membrane; among these agents, SPC has been described as a novel messenger for Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) has recently been reported to inhibit SPC-induced Rho-kinase activation in vitro, and thereby vascular smooth muscle contraction, through the inhibition of Src family protein tyrosine kinases translocation. Moreover, the concentration of AA increases in the cerebrospinal fluid of patients with SAH, suggesting that this substance has a potential role in the occurrence of cerebral vasospasm following SAH, while EPA is known to change the constitution ratios of AA and EPA in cell membrane phospholipid, resulting in the inhibition of TXA2 synthesis. These observations lead us to hypothesize that EPA may inhibit cerebral vasospasm following SAH through the inhibition of Rho-kinase activation.

Study Timeline

• Study Start: 2004-12
• Primary Completion: 2008-06
• Study Completion: 2008-12
• Study First Submitted: 2009-02-04
• Study First Submitted QC: 2009-02-06
• Study First Posted: 2009-02-09
• Status Verified: 2009-09
• Last Update Submitted: 2009-09-01
• Last Update Posted: 2009-09-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Subarachnoid hemorrhage (SAH)
• The ruptured cerebral aneurysms conformed by cerebral angiography
• The patients with treated by craniotomy and clip application within 72h after the onset of SAH

Exclusion Criteria

• Traumatic or mycotic aneurysms
• A history or complication of serious stroke
• Moya Moya disease
• A history of SAH
• Complication of serious heart or hepatic disease or infection or renal failure
• Malignant tumor
• Patients judged to be inappropriate by physician in charge

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Eicosapentaenoic acid ethyl ester	Patients in the group A are orally administered eicosapentaenoic acid ethyl ester.

Primary Outcome Measures

Name	Time	Method
Cerebral vasospasms: Symptomatic vasospasm defined as documented arterial vasospasm consistent with new neurological deterioration. New low-density areas on CT scans associated with vasospasm.	Between 4 and 30 days after the onset of SAH

Secondary Outcome Measures

Name	Time	Method
Patient's Glasgow Outcome Scale (GOS).	At 1 month after onset of SAH.

Trial Locations

Locations (5)

Iwate Medical University; 🇯🇵 Morioka, Iwate, Japan

Yamaguchi University Hospital; 🇯🇵 Ube, Yamaguchi, Japan

Ootemachi Hospital; 🇯🇵 Kitakyushu, Fukuoka, Japan

Nakamura Memorial Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Tohoku University; 🇯🇵 Sendai, Miyagi, Japan