SepsisNCT03133208
Sepsis Associated Encephalopathy (SAE) Biomarkers
An observational study of Sepsis and Altered Mental Status, run by University of Florida at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Altered Mental Status, Sepsis-Associated Delirium
- What is being tested?
- Blood draws
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 15 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Patients who present to UF Health Shands emergency department with sepsis. The sepsis cohort will be further broken down into sub- cohorts: * Cohort 1: Patients who present with altered mental status * Cohort 2: Patients who do not present with altered mental status A control cohort (cohort 3) will include patients presenting to the ED with no suspicion of systemic inflammation that need hospitalization.
Who may be able to join
- 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
Show all 27Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Serum Biomarkers in Sepsis Associated Encephalopathy (SAE)
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.
Read the detailed description
Sepsis associated encephalopathy (SAE) is a common neurological complication of sepsis that is often associated with worse prognosis, yet remains poorly understood. It occurs in the absence of direct brain infection or other types of disease-associated encephalopathy such as hepatic or renal encephalopathy, and is a result of systemic inflammation (1). Clinically, a diagnosis of SAE is made when there is an impaired mental state in the presence of an extracranial infection. Clinical features of SAE include change in mental status (altered mental status/ AMS), disturbances in mental processes, agitation, disorientation, impaired attention, hypersomnolence, delirium or coma. SAE may be an early sign of sepsis that is manifested prior to overt evidence of other organ failures (2), and is an independent prognosticator of morbidity and mortality (3). Moreover, sepsis survivors can suffer from long-term cognitive impairments that impact their quality of life.
The pathophysiology of SAE is a complex constellation of proposed mechanisms that include direct insult to brain tissue from circulating inflammatory mediators that are overexpressed in sepsis, disturbances in metabolic pathways, cellular hypoxia, disruption of the BBB integrity, alterations in neurotransmission, impairment of regulation of the brain perfusion. The consequence of this combination of neuroinflammatory and ischemic processes is neuronal degeneration and cell death (apoptosis).
It is difficult to diagnose SAE early, as sepsis is often a diagnosis of exclusion and can be occult in presentation. For example, emergency physicians may conduct diagnostic studies to evaluate for stroke, metabolic disturbance (i.e. hyponatremia, hypoglycemia, vitamin deficiency, medication reaction), toxicity, seizure or other acute neurologic condition. In addition, severe sepsis patients may be intubated and are often sedated, which poses a challenge to conducting a neurological assessment of their mental status. There may be changes in electroencephalography (EEG), somatosensory-evoked potentials (SSEP), or neuroimaging but these tests lack specificity and SAE remains a diagnosis of exclusion.
Injured neurons release neuron specific proteins that diffuse across the disrupted BBB into the blood and could have diagnostic relevance in diagnosing SAE. Neuron specific enolase (NSE) and S100 beta (S100B) are biomarkers currently used in the setting of SAE and have been studied clinically. There is a lack of human studies on other proteins such as GFAP, co-peptin, Tau, neurofilament light/ heavy chain, UCH-L1, SBDP, MBP, and secretoneurin that have been proposed as potential biomarkers of neurological outcome for other causes of acute brain dysfunction such as traumatic brain injury (TBI) and hypoxic ischemic encephalopathies (HIE) and could potentially serve as candidate biomarkers to diagnose SAE.
Most studies lack a control cohort. The Investigator intends to sample sepsis patients that present to the emergency department but do not develop altered mental status within our study as well.
The Investigator therefore propose a prospective, observational study in which the study team will perform blood biomarker analysis from time of enrollment up to study day 3. This would be done by drawing blood at (0-30mins), and additional blood draws at hours 6, 12, 18, 24, 48, 72. The Investigator will then determine whether biomarker levels correlate with neurologic assessment in the Emergency Department (ED), degree of overall organ dysfunction, survival to hospital admission, survival to hospital discharge, and functional neurologic outcome at discharge and at 6 months.
- Conditions
- Sepsis, Altered Mental Status, Sepsis-Associated Delirium, Sepsis Associated Encephalopathy, Delirium, Sepsis Associated
- Being tested
- Blood draws
- Keywords
- sepsis, sepsis associated encephalopathy, sepsis associated delirium, altered mental status
- Medical subject headings
- Sepsis, Sepsis-Associated Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawsProcedure or surgery
Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72 (7 draws total). Each draw would be up to 20 mL of blood (but no less than 10 mL).
| Study group | Role | What they receive |
|---|---|---|
| Sepsis with AMS | Patients presenting to the ED with suspected sepsis who develop altered mental status Receives: Procedure: Blood draws | |
| Sepsis without AMS | Patients presenting to the ED with suspected sepsis without change in mental status Receives: Procedure: Blood draws | |
| Control | Patients presenting to the ED with no suspicion of systemic inflammation that need hospitalization (control category) Receives: Procedure: Blood draws |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
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]
Measured: 1 year
Secondary outcomes (4)
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.
Measured: 1 year
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.
Measured: 7-day, 28-day, and 6-months mortality
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
Measured: up to 2 weeks
Degree of neurological impairment
Cognitive Failure Questionnaire (CFQ) sum of 25 questions, range 0-100 assessing Forgetfulness, Distractibility, and False Triggering
Measured: 6 months after discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2017
- Study start1 Jun 2017
- Primary completion15 Dec 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie-Carmelle Elie, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03133208
- Sponsor's protocol ID
- IRB201700135
- Status last verified
- Oct 2025
- First submitted
- 10 Apr 2017
- Last updated
- 28 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Chaudhry N, Duggal AK. Sepsis Associated Encephalopathy. Adv Med. 2014;2014:762320. doi: 10.1155/2014/762320. Epub 2014 Sep 30.
PubMed 26556425Bello JH, Park M. Sepsis-associated encephalopathy as a differential diagnosis with motor deficit plus altered mental status. Clinics (Sao Paulo). 2007 Apr;62(2):199-202. doi: 10.1590/s1807-59322007000200017. No abstract available.
PubMed 17505707Sprung CL, Peduzzi PN, Shatney CH, Schein RM, Wilson MF, Sheagren JN, Hinshaw LB. Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit Care Med. 1990 Aug;18(8):801-6. doi: 10.1097/00003246-199008000-00001.
PubMed 2379391Shankar-Hari M, Rubenfeld GD. Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges. Curr Infect Dis Rep. 2016 Nov;18(11):37. doi: 10.1007/s11908-016-0544-7.
PubMed 27709504Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553.
PubMed 20978258Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED. Pathophysiology of septic encephalopathy: a review. Crit Care Med. 2000 Aug;28(8):3019-24. doi: 10.1097/00003246-200008000-00057.
PubMed 10966289Consales G, De Gaudio AR. Sepsis associated encephalopathy. Minerva Anestesiol. 2005 Jan-Feb;71(1-2):39-52. English, Italian.
PubMed 15711505Jacob A, Brorson JR, Alexander JJ. Septic encephalopathy: inflammation in man and mouse. Neurochem Int. 2011 Mar;58(4):472-6. doi: 10.1016/j.neuint.2011.01.004. Epub 2011 Jan 8.
PubMed 21219956Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat. 2002 Jun;200(6):639-46. doi: 10.1046/j.1469-7580.2002.00065.x.
PubMed 12162731Polito A, Eischwald F, Maho AL, Polito A, Azabou E, Annane D, Chretien F, Stevens RD, Carlier R, Sharshar T. Pattern of brain injury in the acute setting of human septic shock. Crit Care. 2013 Sep 18;17(5):R204. doi: 10.1186/cc12899.
PubMed 24047502Zhang QH, Sheng ZY, Yao YM. Septic encephalopathy: when cytokines interact with acetylcholine in the brain. Mil Med Res. 2014 Sep 1;1:20. doi: 10.1186/2054-9369-1-20. eCollection 2014.
PubMed 25722876Szatmari S, Vegh T, Csomos A, Hallay J, Takacs I, Molnar C, Fulesdi B. Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit Care. 2010;14(2):R50. doi: 10.1186/cc8939. Epub 2010 Mar 31.
PubMed 20356365Sharshar T, Annane D, de la Grandmaison GL, Brouland JP, Hopkinson NS, Francoise G. The neuropathology of septic shock. Brain Pathol. 2004 Jan;14(1):21-33. doi: 10.1111/j.1750-3639.2004.tb00494.x.
PubMed 14997934Bozza FA, D'Avila JC, Ritter C, Sonneville R, Sharshar T, Dal-Pizzol F. Bioenergetics, mitochondrial dysfunction, and oxidative stress in the pathophysiology of septic encephalopathy. Shock. 2013 May;39 Suppl 1:10-6. doi: 10.1097/SHK.0b013e31828fade1.
PubMed 23481496Hirota K. Involvement of hypoxia-inducible factors in the dysregulation of oxygen homeostasis in sepsis. Cardiovasc Hematol Disord Drug Targets. 2015;15(1):29-40. doi: 10.2174/1871529x15666150108115553.
PubMed 25567333
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Biomarkers in Sepsis Associated Encephalopathy (SAE)
- ClinicalTrials.gov ID
- NCT03133208
- Acronym / sponsor ID
- IRB201700135
- Conditions
- Sepsis, Altered Mental Status, Sepsis-Associated Delirium, Sepsis Associated Encephalopathy, Delirium, Sepsis Associated
- Keywords
- sepsis, sepsis associated encephalopathy, sepsis associated delirium, altered mental status
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 28 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Sepsis associated encephalopathy (SAE) is a common neurological complication of sepsis that is often associated with worse prognosis, yet remains poorly understood. It occurs in the absence of direct brain infection or other types of disease-associated encephalopathy such as hepatic or renal encephalopathy, and is a result of systemic inflammation (1). Clinically, a diagnosis of SAE is made when there is an impaired mental state in the presence of an extracranial infection. Clinical features of SAE include change in mental status (altered mental status/ AMS), disturbances in mental processes, agitation, disorientation, impaired attention, hypersomnolence, delirium or coma. SAE may be an early sign of sepsis that is manifested prior to overt evidence of other organ failures (2), and is an independent prognosticator of morbidity and mortality (3). Moreover, sepsis survivors can suffer from long-term cognitive impairments that impact their quality of life.
The pathophysiology of SAE is a complex constellation of proposed mechanisms that include direct insult to brain tissue from circulating inflammatory mediators that are overexpressed in sepsis, disturbances in metabolic pathways, cellular hypoxia, disruption of the BBB integrity, alterations in neurotransmission, impairment of regulation of the brain perfusion. The consequence of this combination of neuroinflammatory and ischemic processes is neuronal degeneration and cell death (apoptosis).
It is difficult to diagnose SAE early, as sepsis is often a diagnosis of exclusion and can be occult in presentation. For example, emergency physicians may conduct diagnostic studies to evaluate for stroke, metabolic disturbance (i.e. hyponatremia, hypoglycemia, vitamin deficiency, medication reaction), toxicity, seizure or other acute neurologic condition. In addition, severe sepsis patients may be intubated and are often sedated, which poses a challenge to conducting a neurological assessment of their mental status. There may be changes in electroencephalography (EEG), somatosensory-evoked potentials (SSEP), or neuroimaging but these tests lack specificity and SAE remains a diagnosis of exclusion.
Injured neurons release neuron specific proteins that diffuse across the disrupted BBB into the blood and could have diagnostic relevance in diagnosing SAE. Neuron specific enolase (NSE) and S100 beta (S100B) are biomarkers currently used in the setting of SAE and have been studied clinically. There is a lack of human studies on other proteins such as GFAP, co-peptin, Tau, neurofilament light/ heavy chain, UCH-L1, SBDP, MBP, and secretoneurin that have been proposed as potential biomarkers of neurological outcome for other causes of acute brain dysfunction such as traumatic brain injury (TBI) and hypoxic ischemic encephalopathies (HIE) and could potentially serve as candidate biomarkers to diagnose SAE.
Most studies lack a control cohort. The Investigator intends to sample sepsis patients that present to the emergency department but do not develop altered mental status within our study as well.
The Investigator therefore propose a prospective, observational study in which the study team will perform blood biomarker analysis from time of enrollment up to study day 3. This would be done by drawing blood at (0-30mins), and additional blood draws at hours 6, 12, 18, 24, 48, 72. The Investigator will then determine whether biomarker levels correlate with neurologic assessment in the Emergency Department (ED), degree of overall organ dysfunction, survival to hospital admission, survival to hospital discharge, and functional neurologic outcome at discharge and at 6 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sepsis with AMS | – | Procedure: Blood drawsPatients presenting to the ED with suspected sepsis who develop altered mental status |
| Sepsis without AMS | – | Procedure: Blood drawsPatients presenting to the ED with suspected sepsis without change in mental status |
| Control | – | Procedure: Blood drawsPatients presenting to the ED with no suspicion of systemic inflammation that need hospitalization (control category) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who present to UF Health Shands emergency department with sepsis. The sepsis cohort will be further broken down into sub- cohorts: * Cohort 1: Patients who present with altered mental status * Cohort 2: Patients who do not present with altered mental status A control cohort (cohort 3) will include patients presenting to the ED with no suspicion of systemic inflammation that need hospitalization.
Key inclusion criteria (27 listed)
- ≥ 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
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Blood drawsBlood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72 (7 draws total). Each draw would be up to 20 mL of blood (but no less than 10 mL). | Procedure or surgery | Control, Sepsis with AMS, Sepsis without AMS |
Primary outcome
Relationship between biomarkers and neurological outcome- Delirium
Time frame: 1 year
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.
Relationship between biomarkers and neurological outcome - Blessed
Time frame: 1 year
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]
4 secondary outcomes
Relationship between biomarkers and organ dysfunction
Time frame: 1 year
Relationship between biomarkers and overall survival
Time frame: 7-day, 28-day, and 6-months mortality
Degree of neurological impairment
Time frame: up to 2 weeks
Degree of neurological impairment
Time frame: 6 months after discharge
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2025.
- Background: PubMed 26556425Chaudhry N, Duggal AK. Sepsis Associated Encephalopathy. Adv Med. 2014;2014:762320. doi: 10.1155/2014/762320. Epub 2014 Sep 30.
- Background: PubMed 17505707Bello JH, Park M. Sepsis-associated encephalopathy as a differential diagnosis with motor deficit plus altered mental status. Clinics (Sao Paulo). 2007 Apr;62(2):199-202. doi: 10.1590/s1807-59322007000200017. No abstract available.
- Background: PubMed 2379391Sprung CL, Peduzzi PN, Shatney CH, Schein RM, Wilson MF, Sheagren JN, Hinshaw LB. Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit Care Med. 1990 Aug;18(8):801-6. doi: 10.1097/00003246-199008000-00001.
- Background: PubMed 27709504Shankar-Hari M, Rubenfeld GD. Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges. Curr Infect Dis Rep. 2016 Nov;18(11):37. doi: 10.1007/s11908-016-0544-7.
- Background: PubMed 20978258Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553.
- Background: PubMed 10966289Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED. Pathophysiology of septic encephalopathy: a review. Crit Care Med. 2000 Aug;28(8):3019-24. doi: 10.1097/00003246-200008000-00057.
- Background: PubMed 15711505Consales G, De Gaudio AR. Sepsis associated encephalopathy. Minerva Anestesiol. 2005 Jan-Feb;71(1-2):39-52. English, Italian.
- Background: PubMed 21219956Jacob A, Brorson JR, Alexander JJ. Septic encephalopathy: inflammation in man and mouse. Neurochem Int. 2011 Mar;58(4):472-6. doi: 10.1016/j.neuint.2011.01.004. Epub 2011 Jan 8.
- Background: PubMed 12162731Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat. 2002 Jun;200(6):639-46. doi: 10.1046/j.1469-7580.2002.00065.x.
- Background: PubMed 24047502Polito A, Eischwald F, Maho AL, Polito A, Azabou E, Annane D, Chretien F, Stevens RD, Carlier R, Sharshar T. Pattern of brain injury in the acute setting of human septic shock. Crit Care. 2013 Sep 18;17(5):R204. doi: 10.1186/cc12899.
- Background: PubMed 25722876Zhang QH, Sheng ZY, Yao YM. Septic encephalopathy: when cytokines interact with acetylcholine in the brain. Mil Med Res. 2014 Sep 1;1:20. doi: 10.1186/2054-9369-1-20. eCollection 2014.
- Background: PubMed 20356365Szatmari S, Vegh T, Csomos A, Hallay J, Takacs I, Molnar C, Fulesdi B. Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit Care. 2010;14(2):R50. doi: 10.1186/cc8939. Epub 2010 Mar 31.
- Individual participant dataSharing planned: Undecided
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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.
Marie-Carmelle Elie, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Altered Mental Status, run by University of Florida 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 27 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Relationship between biomarkers and neurological outcome- Delirium (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT03133208, which also lists 20 linked publications.
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 28 Oct 2025.