Clinical Trials Directory

Trials / Completed

CompletedNCT03318783

Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial

Status
Completed
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
20 (actual)
Sponsor
Oregon Health and Science University · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypotheses: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability in the blood and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and efficacy of GSK2256294, a novel soluble epoxide hydrolase inhibitor in patients with aneurysmal SAH.

Detailed description

Study Description: Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypothesis: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability at the neurovascular unit, and a measured increase in the EET/DHET ratio in the serum and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and of GSK2256294, an inhibitor of soluble epoxide hydrolase, in patients with aneurysmal SAH. Objectives: Primary Objective: Determine the safety of administration of GSK2256294 in patients with aneurysmal SAH. Secondary Objective: Determine the pharmacodynamic effect of administration of GSK2256294 in patients with aneurysmal SAH on reducing EETs metabolism and biomarkers of cerebrovascular inflammation and endothelial injury. Tertiary Objective: Provide preliminary estimates of clinical endpoints to inform the design of a larger trial Endpoints: Primary Endpoints: Determination of safety Secondary endpoints: 1. Study days 7 and 10 serum EET/DHET ratios 2. Study days 7 and 10 cerebrospinal fluid (CSF) EET/DHET ratios 3. Study days 7 and 10 serum EPOME/DPOME ratio 4. Neuroinflammatory and endothelial injury biomarker levels from the blood and CSF at day 7 and day 10. Tertiary, exploratory endpoints: Clinical outcomes associated with SAH including neurologic status, disposition, vital status and incidence of delayed cerebral ischemia. 20 subjects will be randomized. Patients age 18 or above with confirmed ruptured aneurysms will be approached to provide written informed consent Phase: Phase 1B Description of Sites/Facilities Enrolling Participants: The study will take place at Oregon Health \& Science University Hospital, with enrollment of patients admitted to the OHSU NSICU, a part of a comprehensive stroke center certified by the American Heart Association and Joint Commission for Accreditation of Healthcare Organizations, with a catchment area including the state of Oregon, Southwest Washington and Northern California. Approximately 80-100 patients with aneurysmal SAH are admitted each year. Description of Study Intervention: Twenty patients will be equally randomized to receive once daily either 10 mg dose of GSK2256294 or placebo enterally for a duration of 10 days. Study Duration: 24 months Participant Duration: 90 days

Conditions

Interventions

TypeNameDescription
DRUGGSK2256294GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days.
DRUGPlaceboPlacebo will be administered in a single dose once daily enteral for a duration of 10 days.

Timeline

Start date
2018-05-02
Primary completion
2019-04-03
Completion
2020-01-09
First posted
2017-10-24
Last updated
2021-01-22
Results posted
2021-01-22

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03318783. Inclusion in this directory is not an endorsement.