Subarachnoid Hemorrhage, AneurysmalPhase 1/2SUSHINCT03318783
Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
A Phase 1/2 study testing GSK2256294 in people with Subarachnoid Hemorrhage, Aneurysmal and Delayed Cerebral Ischemia, run by Oregon Health and Science University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Vasospasm, Cerebral
- What is being tested?
- GSK2256294
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2018to 9 Jan 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18
- Head CT evidence of subarachnoid hemorrhage
- Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.
Who cannot join
- Symptom onset compatible with SAH of > 3 days prior to admission to OHSU
- Absence of an indwelling external ventricular drain
- Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
- Suspected or confirmed pregnancy
- Preexisting severe neurologic deficit or condition
- Chronic renal failure requiring dialysis
Show all 9Show fewer
- Severe terminal disease with life expectancy <6 months
- Unable to read or understand written or spoken English or Spanish
- Refusal of informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
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.
Read the 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:
- Study days 7 and 10 serum EET/DHET ratios
- Study days 7 and 10 cerebrospinal fluid (CSF) EET/DHET ratios
- Study days 7 and 10 serum EPOME/DPOME ratio
- 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
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Vasospasm, Cerebral, Endothelial Dysfunction
- Being tested
- GSK2256294, Placebo
- Keywords
- Eicosanoids, Epoxyeicosatrienoic Acids
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2256294Drug
GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days.
PlaceboDrug
Placebo will be administered in a single dose once daily enteral for a duration of 10 days.
| Study group | Role | What they receive |
|---|---|---|
| GSK2256294 | Active comparator | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. Receives: Drug: GSK2256294 |
| Placebo | Placebo comparator | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With Adverse Events
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.
Measured: 90 days
Secondary outcomes (4)
Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL)
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.
Measured: 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)
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.
Measured: 10 days
Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10
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).
Measured: 10 days
CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10
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)
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start2 May 2018
- Primary completion3 Apr 2019
- Study completion9 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to one of the two treatment arms based on an unrestricted or "fair-coin" randomization procedure.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, GlaxoSmithKline
- Responsible party
- Principal investigator, Ross Martini, MD, Oregon Health and Science University
- Investigators
- Ross Martini, MD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318783
- Sponsor's protocol ID
- 17614
- Acronym
- SUSHI
- Status last verified
- Dec 2020
- First submitted
- 10 Oct 2017
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Martini RP, Siler D, Cetas J, Alkayed NJ, Allen E, Treggiari MM. A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2022 Jun;36(3):905-915. doi: 10.1007/s12028-021-01398-8. Epub 2021 Dec 6.
PubMed 34873674
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
- ClinicalTrials.gov ID
- NCT03318783
- Acronym / sponsor ID
- SUSHI / 17614
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Vasospasm, Cerebral, Endothelial Dysfunction
- Keywords
- Eicosanoids, Epoxyeicosatrienoic Acids
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, GlaxoSmithKline
- Study start
- 2 May 2018 (actual)
- Primary completion
- 3 Apr 2019 (actual)
- Study completion
- 9 Jan 2020 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Posted 22 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Study days 7 and 10 serum EET/DHET ratios
- Study days 7 and 10 cerebrospinal fluid (CSF) EET/DHET ratios
- Study days 7 and 10 serum EPOME/DPOME ratio
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized to one of the two treatment arms based on an unrestricted or "fair-coin" randomization procedure.
| Arm | Type | Receives |
|---|---|---|
| GSK2256294 | Active comparator | Drug: GSK225629410mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. |
| Placebo | Placebo comparator | Drug: Placebo10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18
- Head CT evidence of subarachnoid hemorrhage
- Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.
Key exclusion criteria (9 listed)
- Symptom onset compatible with SAH of > 3 days prior to admission to OHSU
- Absence of an indwelling external ventricular drain
- Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
- Suspected or confirmed pregnancy
- Preexisting severe neurologic deficit or condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2256294GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. | Drug | GSK2256294 |
| PlaceboPlacebo will be administered in a single dose once daily enteral for a duration of 10 days. | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) 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, by Mass Spectroscopic Analysis (ng/mL)
Time frame: 10 days
Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10
Time frame: 10 days
CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10
Time frame: 10 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34873674Martini RP, Siler D, Cetas J, Alkayed NJ, Allen E, Treggiari MM. A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2022 Jun;36(3):905-915. doi: 10.1007/s12028-021-01398-8. Epub 2021 Dec 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ross Martini, MD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GSK2256294 in people with Subarachnoid Hemorrhage, Aneurysmal and Delayed Cerebral Ischemia, run by Oregon Health and Science University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With Adverse Events (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03318783, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.