NCT00839449

Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study

Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS): Effect of Eicosapentaenoic Acid on Cerebral Vasospasm Following Subarachnoid Hemorrhage

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 200 (actual)
• Sponsor: Yamaguchi University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Subarachnoid Hemorrhage
• Cerebral Vasospasm

Interventions

Type	Name	Description
DRUG	Eicosapentaenoic acid ethyl ester	Orally administered 900 mg eicosapentaenoic acid ethyl ester three times a day (2700 mg ⁄ day) from the surgery next day to 30 days after the onset of SAH.

Timeline

• Start date: 2004-12-01
• Primary completion: 2008-06-01
• Completion: 2008-12-01
• First posted: 2009-02-09
• Last updated: 2009-09-03

Locations

5 sites across 1 country: Japan