Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial (SUSHI)

December 31, 2020 updated by: Ross Martini, MD, Oregon Health and Science University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age > 18
  2. Head CT evidence of subarachnoid hemorrhage
  3. Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.

Exclusion Criteria:

  1. Symptom onset compatible with SAH of > 3 days prior to admission to OHSU
  2. Absence of an indwelling external ventricular drain
  3. Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
  4. Suspected or confirmed pregnancy
  5. Preexisting severe neurologic deficit or condition
  6. Chronic renal failure requiring dialysis
  7. Severe terminal disease with life expectancy <6 months
  8. Unable to read or understand written or spoken English or Spanish
  9. Refusal of informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: GSK2256294
10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days.
Drug: GSK2256294
GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days.
Placebo Comparator: Placebo
10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days.
Drug: Placebo
Placebo will be administered in a single dose once daily enteral for a duration of 10 days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Participants With Adverse Events
Time Frame: 90 days

Summary tables and listings will be provided for all reported adverse events, defined as adverse events that start on or after the first administration of study drug. The reported adverse event term will be assigned a standardized preferred term.

Adverse events will be summarized based on the number and percentage of patients experiencing the event. In the event a patient experiences repeat episodes of the same adverse event, then the event with the highest severity grade and strongest causal relationship to study treatment will be used for purposes of incidence tabulations.

All deaths will be reported in a patient listing, which will include the primary cause of death and the number of days between the date of the last dose of study drug and death.
90 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL)
Time Frame: 10 days

Day 7 and day 10 serum EET/DHET ratios will be measured by liquid chromatography and mass spectroscopy of collected blood samples.

Day 7 and day 10 CSF EET/DHET ratios will be measured by liquid chromatography and mass spectroscopy of collected CSF samples.
10 days
Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL)
Time Frame: 10 days
Study day 7 and study day 10 serum epoxyoctadecenoic acid (EPOME) to dihydroxyoctadec-12-enoic acid (DPOME) ratio, will be measure by mass spectroscopic analysis of collected blood samples.
10 days
Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10
Time Frame: 10 days
The following serum biomarkers will be obtained from collected blood samples by Luminex assay: e-selectin, p-selectin, Vascular cell adhesion marker (VCAM-1), Platelet endothelial cell adhesion marker (PECAM-1, CD31), intercellular adhesion molecule (ICAM-1).
10 days
CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10
Time Frame: 10 days
The following CSF biomarker will be obtained from collected CSF samples by Luminex assay: Tumor necrosis factor alpha (TNF-α) (pg/mL), Interleukin 1β (IL-1β) (pg/mL), Interferon gamma (IFN-γ) (pg/mL), Interleukin 6 (IL-6) (pg/mL), Interleukin 8 (IL-8) (pg/mL), Monocyte chemoattractant protein 1 (MCP-1) (pg/mL)
10 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital Length of Stay in Days
Time Frame: 90 days
The hospital length of stay will be recorded in days, at the time of hospital discharge.
90 days
Discharge Disposition
Time Frame: 90 days
The disposition from the hospital in one of the following categories: home, home with services, rehab, long term acute care facility, skilled nursing facility, hospice, death
90 days
Number of Participants With New Stroke on Hospital Discharge Imaging
Time Frame: 90 days
The last head CT or other brain imaging to detect the presence of a new area of cerebral infarction will be reviewed at the time of hospital discharge. A cerebral infarction will be defined as a one identified on hospital discharge that was not present on imaging between 24-48 hours after aneurysm occlusion, and not attributable to other causes such as surgical clipping or endovascular treatment. Hypodensities resulting from extraventricular drains or residual intraparencyhmal hematomas will not be considered new strokes.
90 days
Modified Rankin Scale (mRS) at Hospital Discharge and 90 Day Follow up
Time Frame: 90 days
The mRS score will be determined by patient or surrogate interview, at both hospital discharge and 90 day follow up. Scores will be assigned based on the following: 0 - no symptoms, 1 - no significant disability, able to carry out all usual activities despite some symptoms, 2 - slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 - moderate disability, requires some help, but able to walk unassisted, 4 - moderately severe disability, unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 - severe disability, requires constant nursing care and attention, bedridden, incontinent, 6 - deceased.
90 days
Extended Glasgow Outcome Scale (GOSE) Score at 90 Day Follow up
Time Frame: 90 days
At 90 day follow up, the GOSE will be determined by patient or surrogate telephone interview, based on a structured interview of 19 questions. The GOSE is a scale of 1-8 where 1 - deceased, 2 - vegetative state, 3 - low severe disability, 4 - upper severe disability, 5 - low moderate disability, 6 -upper moderate disability, 7 - low good recovery, 8 - upper good recovery.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Oregon Health and Science University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline
Foundation for Anesthesia Education and Research

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ross Martini, MD, Oregon Health and Science University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 2, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 9, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 31, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17614

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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