Sepsis Clinical Trial
Official title:
Serum Biomarkers in Sepsis Associated Encephalopathy (SAE)
Verified date | January 2024 |
Source | University of Florida |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
Sepsis associated encephalopathy (SAE) is a poorly understood acute cerebral dysfunction that frequently appears in the setting of sepsis induced systemic inflammation. In fact, altered mentation is recognized as an independent predictor of death and poor outcomes in patients with sepsis. SAE may be manifested by a number of symptoms characterized by a change in baseline behavior, attention, alertness, cognition, or executive functioning. It occurs in the absence of direct Central Nervous System (CNS) infection, and the exact pathophysiology is of SAE is unknown, but theoretically seems to encompass a constellation of mechanisms such as impairment of the blood brain barrier (BBB), endothelial dysfunction, alteration in cerebral blood flow and neurotransmission, circulating inflammatory mediators, cellular hypoxia, and metabolic disturbances, that ultimately result in neuronal dysfunction and cell death. SAE is characterized by an altered mental status (AMS) that ranges from delirium to coma, and can lead to long-term cognitive impairment. SAE may appear early in the course of sepsis, and is often underestimated as an independent factor of mortality, yet the pathophysiology of SAE remains unknown, and there is a lack of specific investigations available to clinicians. Studies have evaluated biomarkers as prognostic tools. The Investigator propose to measure neuron specific enolase (NSE), S-100B, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), Tau protein, Copeptin, spectrin breakdown products (SBDP 145, SBDP150), αII-spectrin N-terminal fragment (SNTF), neurofilament light and heavy chains (NF-L, NF-H), myelin basic protein (MBP), secretoneurin (SN), and other peptide levels in the serum of sepsis patients who develop altered mental status, to evaluate the kinetics of said biomarkers for 72 hours. The Investigator will monitor the course of the patients' hospitalization to determine whether there are biomarker correlates with survival and outcomes, including neurologic impairment. Finally, this investigation may provide a mechanistic pathway that defines the development of AMS in septic patients.
Status | Active, not recruiting |
Enrollment | 90 |
Est. completion date | July 6, 2025 |
Est. primary completion date | July 6, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Cohort 1: - = 18 years old - Presented to the emergency department at Shands - Has not donated blood within the last 8 weeks - Willing to participate and follow up at 6 months after discharge from the hospital - Not anemic or have any other hematological disorders that requires transfusions Meets two or more Systemic Inflammatory Response Syndrome (SIRS) criteria: - Temperature >38°C or <36°C - Heart rate (HR) > 90bpm - Respiratory rate (RR) > 20bpm or partial pressures of carbon dioxide (PaCO2) <32mm mercury (HG) - White Blood Cell (WBC) >12,000/µL or < 4,000/µL or >10% immature/ bands Clinical suspicion of sepsis (blood cultures ordered/ antibiotics started) Altered mental status Enrolled within 6 hours of ED presentation Cohort 2 - = 18 years old - Presented to the emergency department at Shands - Has not donated blood within the last 8 weeks - Willing to participate and follow up at 6 months after discharge from the hospital - Not anemic or have any other hematological disorders that requires transfusions Meets two or more SIRS criteria: - Temperature >38°C or <36°C - HR > 90bpm - RR > 20bpm or PaCO 2 <32mmHG - WBC >12,000/µL or < 4,000/µL or >10% immature/ bands Clinical suspicion of sepsis (blood cultures ordered/ antibiotics started) No altered mental status Enrolled within 6 hours of ED presentation Cohort 3 (control) - Does not meet SIRS criteria - No clinical suspicion of sepsis (no cultures/ antibiotics ordered) - Not altered - Patient has admission orders Exclusion Criteria (all cohorts): - Participating in another interventional, therapeutic study that may affect the results of this study - Subject has neurodegenerative disease or other neurological disorder (dementia, Parkinson's disease, multiple sclerosis, seizure disorder, or brain tumours) - History of neurosurgery within the last 30 days - Acute brain injury within the last 30 days (ischemic/ haemorrhagic stroke, traumatic brain injury) - Subject is anemic OR donated blood within the last 8 weeks OR has a hematological disorder that requires transfusions - Subject has history of liver failure OR renal failure - Pregnant or lactating female |
Country | Name | City | State |
---|---|---|---|
United States | University of Florida | Gainesville | Florida |
Lead Sponsor | Collaborator |
---|---|
University of Florida |
United States,
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* Note: There are 20 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Relationship between biomarkers and neurological outcome- Delirium | Acute encephalopathy will be measured using the mental status assessment including the Delirium Triage Screen (DTS) Brief Confusion Assessment Method (bCAM). DTS-bCAM assessment is a flowchart that helps diagnose a patient who is altered. | 1 year | |
Primary | Relationship between biomarkers and neurological outcome - Blessed | Acute encephalopathy will be measured using the mental status assessment short blessed test (SBT). Sum Total (range 0-28) [0-4 = normal cognition, 5-9 = questionable impairment, = 10 = Impairment consistent with dementia] | 1 year | |
Secondary | Relationship between biomarkers and organ dysfunction | Organ dysfunction will be assessed using Sequential Organ Failure Assessment (SOFA) methodology, a mortality assessment tool that monitors the dynamics of cardiovascular, respiratory, neurological, renal, hepatic, and hematological organ function. | 1 year | |
Secondary | Relationship between biomarkers and overall survival | Date of death will be recorded for all patients who died during the study period. Rate of survival will be assessed. | 7-day, 28-day, and 6-months mortality | |
Secondary | Degree of neurological impairment | assessed using the Cerebral Performance Category (CPC) scoring [CPC 1: A return to normal cerebral function and normal living, CPC 2: Cerebral disability but sufficient function for independent activities of daily living, CPC 3: Severe disability, limited cognition, inability to carry out independent existence, CPC 4: Coma, CPC 5: Brain death | up to 2 weeks | |
Secondary | Degree of neurological impairment | Cognitive Failure Questionnaire (CFQ) sum of 25 questions, range 0-100 assessing Forgetfulness, Distractibility, and False Triggering | 6 months after discharge |
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