Fargo, North Dakota 58104


Purpose:

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.


Study summary:

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.


Criteria:

This study will not involve cognitively impaired adults, children, neonates, pregnant women or prisoners. Inclusion Criteria: - Have onset of stroke symptoms within 8-hours of presentation (AIS arm only). - 18-years old and older. - Able to offer informed consent after passing the MMSE with score >18. - Participants must be admitted to the hospital and stay for at least 24 hours. - Present with a traumatic or non AIS-related brain injury (non-AIS brain injury arm only). - Diagnosed with non-neurological pathology (non-neurological pathology arm only). Exclusion Criteria: - Have onset of stroke symptoms more than 8-hours before presentation. - Less than 18-years old. - MMSE score 17 or less. - Not able to offer informed consent due to MMSE score of 17 or less - If they leave the hospital within 24 hours after being admitted. - No longer meeting the eligibility criteria.


NCT ID:

NCT03618290


Primary Contact:

Principal Investigator
Vitaliy Starosta, MD
Sanford Health

Richard Lefevre, MS
Phone: 605-404-4290
Email: richard.lefevre@sanfordhealth.org


Backup Contact:

N/A


Location Contact:

Fargo, North Dakota 58104
United States

Elizabeth Eidenschink, MS
Phone: 701-234-6298
Email: Elizabeth.Eidenschink@SanfordHealth.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: February 04, 2019

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