Endothelial Dysfunction Clinical Trial
Official title:
Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
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 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 ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02122198 -
Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women
|
N/A | |
Completed |
NCT04156711 -
Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery
|
N/A | |
Recruiting |
NCT06133634 -
Fisetin to Improve Vascular Function in Older Adults
|
Phase 1/Phase 2 | |
Completed |
NCT05872139 -
Role of Mitochondrial-derived Oxidative Stress to Promote Vascular Endothelial Dysfunction in Non-exercisers With Aging
|
N/A | |
Recruiting |
NCT04558450 -
Covid-19 Effects on Arterial Stiffness and Vascular Aging (CARTESIAN)
|
N/A | |
Terminated |
NCT03325933 -
Resistance Training and Cardiometabolic Health
|
N/A | |
Not yet recruiting |
NCT05939934 -
Impact of the Mandibular Advancement Device on Sleep Apnea During CPAP Withdrawal
|
N/A | |
Completed |
NCT02652975 -
Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium
|
N/A | |
Recruiting |
NCT02334839 -
The Association Between Severity of Hypertensive Disorder During Pregnancy and Endothelial Dysfunction
|
N/A | |
Recruiting |
NCT02020044 -
Outcome After Descemet Membrane Endothelial Keratoplasty (DMEK) and Ultra-thin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)
|
N/A | |
Completed |
NCT01775865 -
Targeting Inflammation to Treat Cardiovascular Aging
|
Phase 2 | |
Completed |
NCT01691404 -
Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)
|
N/A | |
Terminated |
NCT01412216 -
The Effects of Sedentarism on Vascular Function, Inflammation, and Insulin Resistance
|
Phase 2 | |
Completed |
NCT01319344 -
Effect of Eplerenone on Endothelial Function in Metabolic Syndrome
|
Phase 3 | |
Completed |
NCT00987974 -
Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
|
Phase 4 | |
Completed |
NCT00990730 -
Atherosclerosis in Rheumatoid Arthritis
|
N/A | |
Completed |
NCT00848302 -
Endothelial Function in Human Arteries
|
Early Phase 1 | |
Completed |
NCT00532844 -
A Phase 2, Pharmacokinetic (PK) Study of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction
|
Phase 2 | |
Completed |
NCT00376246 -
Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
|
Phase 4 | |
Completed |
NCT00775099 -
Combustion Derived Air Pollution and Vascular Function
|
N/A |