Clinical Trials Logo

Clinical Trial Summary

The purpose of the research is to use plasma free fatty acid profiling as a biomarker for ischemic stroke. The plasma free acid profile will be specifically and significantly changed in early stages upon stroke onset, and correlate with the stroke volume and progression determined by imaging techniques.


Clinical Trial Description

Ischemic stroke is the third leading cause of death and the leading cause of long-term disability in the United States. Immediate treatment can play a major role in the outcome of ischemic stroke and can help improve prognosis in many cases. One of the factors effecting immediate treatment is a rapid and accurate diagnostics of ischemic stroke.

Although imaging techniques remain to be the primary diagnostic instrumental tool, advanced imaging studies can slow management decisions and are sometimes unavailable. In addition, imaging studies often cannot discriminate between pre-existing lesions and acute or ongoing processes. Thus, additional diagnostic and prognosis tools such as plasma biomarkers will be beneficial for the early management of ischemic stroke. Importantly, the only FDA approved therapeutic treatment for ischemic stroke is tPA administration within 3-4.5 hours of stroke onset. Thus, the ideal biomarker for ischemic stroke would be readily detectible within this window for intravenous thrombolysis.

To date, the majority of potential stroke biomarkers studied are of peptide/protein nature and do not meet this requirement. One of the reasons is that hydrophilic substrates including peptides and proteins do not readily cross blood-brain barrier (BBB). Thus, brain specific peptides/proteins are unlikely to be significantly increased in plasma within the therapeutic windows of acute stroke conditions, but rather will be slowly increased during progression of stroke associated with BBB integrity loss. As a result, the most commonly utilized brain-specific protein biomarkers, including S100b and neuron specific enolase, do not increase in plasma before 10-18 hours, and do not correlate with infarct volume prior to 24 hours after injury. Many other brain-specific proteins studied have similar limitations, while proteins such as copeptin found elevated under acute stroke conditions are highly non-specific for the brain and may serve as a more general marker of physiologic stress. Another promising approach is utilization of blood gene expression analysis to identify the etiology of acute ischemic stroke. However, the timing of RNA expression measurement, as well as dynamics for RNA expression may add limitations to this approach to meet "the ideal ischemic stroke biomarker" requirement.

Alternatively, lipid biomarkers may overcome these limitations. Lipids are hydrophobic and readily cross the BBB, are very abounded accounting for about 10% of brain wet weight, have a brain specific profile, and alterations in brain lipids develop immediately upon ischemic injury. Recently, using a targeted quantification, a brain specific sphingolipid was identified as a promising biomarker for acute brain damage, demonstrating a feasibility of using lipid biomarkers to diagnose stroke.

In the current project, the investigators propose a novel approach of using plasma free fatty acid profiling as a biomarker for ischemic stroke. This novel approach is based on well documented features of brain lipid composition and metabolism under acute ischemia conditions. First, the brain has a unique signature of phospholipid fatty acid composition that is different from plasma and other tissues with one of the highest arachidonic, docosahexaenoic, and adrenic acid concentrations, that make up to 20% of fatty acids in the mammalian brain. These polyunsaturated fatty acids are mainly esterified in the sn-2 position on phospholipids and are released by a phospholipase of the A2 family. Secondly, lipids constitute more than half of the dry weight in human brain, making it the second greatest lipid containing organ in the body after adipose tissue, thus representing a significant potential source for fatty acids. Third, upon acute ischemic injury, brain phospholipases (predominantly A2 family) are immediately activated, leading to a rapid (within minutes) release of polyunsaturated fatty acids from sn-2 position from phospholipids in the free form. Because of the hydrophobicity of fatty acids, they are readily permeable for BBB and are expected to be found in plasma. Forth, dietary fatty acids are circulated in the esterified form, while released from adipose tissue free fatty acids have a different fatty acid profile, making brain free fatty acids distinguishable from other fatty acid pools in plasma.

The only FDA approved treatment for ischemic strokes is tissue plasminogen activator (tPA, also known as IV rtPA, given through an IV in the arm), administered within 3-4.5 hours of stroke onset. tPA works by dissolving the clot and improving blood flow to the part of the brain being deprived of blood flow. Although imaging techniques remain to be the primary diagnostic instrumental tool, advanced imaging studies can slow management decisions and are sometimes unavailable. In addition, imaging studies often cannot discriminate between pre-existing lesions and acute or ongoing processes. Thus, additional diagnostic and prognosis tools such as plasma biomarkers will be beneficial for the early management of ischemic stroke. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03618290
Study type Observational
Source Sanford Health
Contact Richard Lefevre, MS
Phone 605-404-4290
Email richard.lefevre@sanfordhealth.org
Status Not yet recruiting
Phase
Start date August 30, 2018
Completion date July 11, 2019

See also
  Status Clinical Trial Phase
Recruiting NCT03574038 - Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke N/A
Recruiting NCT03679637 - Tablet-based Aphasia Therapy in the Acute Phase After Stroke N/A
Recruiting NCT03633422 - Evaluation of Stroke Patient Screening
Recruiting NCT03132558 - Contrast Induced Acute Kidney in Patients With Acute Stroke N/A
Recruiting NCT02541578 - Physiological Complexity of Gait Over the First Six Months Post Stroke N/A
Recruiting NCT02893631 - Assessment of Hemostasis Disorders in rtPA-treated Patients Requiring Endovascular Treatment for Ischemic Stroke
Active, not recruiting NCT02274727 - Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study
Recruiting NCT02225730 - Imaging Collaterals in Acute Stroke (iCAS)
Terminated NCT01705353 - The Role of HMGB-1 in Chronic Stroke N/A
Active, not recruiting NCT01581502 - SAMURAI-NVAF Study: Anticoagulant Therapy for Japanese Stroke Patients With Nonvalvular Atrial Fibrillation (NVAF) N/A
Completed NCT01182818 - Fabry and Stroke Epidemiological Protocol (FASEP): Risk Factors In Ischemic Stroke Patients With Fabry Disease N/A
Completed NCT00761982 - Autologous Bone Marrow Stem Cells in Middle Cerebral Artery Acute Stroke Treatment. Phase 1/Phase 2
Completed NCT00535197 - Autologous Bone Marrow Stem Cells in Ischemic Stroke. Phase 1/Phase 2
Terminated NCT00132509 - FRALYSE Trial: Comparison of the Classical Rt-PA Procedure With a Longer Procedure in Acute Ischemic Stroke Phase 2
Recruiting NCT03235271 - Pilot Study of Acute Stroke Using the Brainpulseâ„¢
Not yet recruiting NCT03592563 - CUHK Brain Health Longitudinal Study
Recruiting NCT03634748 - Thrombolysis in stRoke With Unknown onSet Based on noncontrasT CT
Recruiting NCT03324321 - Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage N/A
Not yet recruiting NCT03641963 - aICP Measurement in Patients With Cerebral Artery Infarction / aICP MCA Infarction N/A
Recruiting NCT02989376 - Carotid Duplex Ultrasound for Selecting Patients for Endovascular Thrombectomy in Acute Stroke Patients N/A