Clinical trial NCT03724201: Neuronal Damage In Delirium Study
Official title: Delirium Severity, Subsyndromal Delirium, and Inflammation-associated Biomarkers in Mechanically Ventilated Patients With Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Delirium
Keywords: Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Biomarkers
Pathophysiology
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2018-10-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Mechanically ventilated patients with sepsis will be recruited from the largest adult ICU in Calgary, Alberta Foothills Medical Centre (FMC).

Brief summary: The purpose of this study is to evaluate associations between neuronal damage biomarkers (S100 calcium-binding protein beta \[S-100β\], neuron-specific enolase \[NSE\], ubiquitin carboxy-terminal hydrolase L1 \[UCHL1\], and brain-derived neurotropic factor \[BDNF\]) and delirium severity and subsyndromal delirium in a homogeneous population of mechanically ventilated patients with sepsis.

Detailed description: Due to high levels of inflammation, patients with sepsis are especially at risk of developing delirium, an organic state of confusion that affects over 80% of mechanically ventilated patients during their intensive care stay. A growing body of literature suggests that the severity of delirium symptoms may also have a significant impact on negative outcomes associated with delirium, including mortality, length of hospital stay, duration of mechanical ventilation, and functional and cognitive impairment. Similarly, recent literature suggests that patient outcomes may be worsened by a subthreshold severity level of delirium, known as subsyndromal delirium. Despite the urgent need to understand delirium and subsyndromal delirium etiology for better detection and management strategies, the multifactorial pathophysiology of delirium is still largely unknown. Clinical biomarker studies evaluating levels of S100 calcium-binding protein beta (S-100β), neuron-specific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and brain-derived neurotropic factor (BDNF) have suggested evidence for their role in delirium pathophysiology, but significant associations with delirium severity and subsyndromal delirium have not been reliably established. Evaluating the dose-response relationship of S-100β, NSE, UCHL1, and BDNF with delirium severity and subsyndromal delirium in a homogeneous population of mechanically ventilated patients with sepsis will provide novel insight on the etiological pathway of delirium. The investigators will evaluate effect modification and confounding by inflammation and blood-brain barrier permeability by measuring well-established biomarkers, interleukin-6 (IL-6) and E-selectin, respectively. Understanding the role of neuronal damage in delirium may be a promising avenue to develop better screening practices and neuroprotective management strategies that may reduce long-term cognitive and functional deficits associated with delirium.

Eligibility criteria: Inclusion Criteria:

* Located in FMC ICU
* Able to consent or have a surrogate decision-maker able to consent
* Richmond Agitation and Sedation Scale Score ≥ -3
* Glasgow Coma Scale (GCS) score ≥ 9
* Able to communicate with the study team (English language, no hearing impairments)
* Expected to remain in the ICU longer than 24 hours
* Sequential Organ Failure Assessment (SOFA) score ≥2 (indicates sepsis based off of Sepsis 3 Guidelines)
* Invasively mechanically ventilated

Exclusion Criteria:

Neurological injury or neurodegenerative condition

Primary outcomes:
measure: Delirium severity and subsyndromal delirium
timeFrame: Up to five days
measure: Serum concentrations of serum S-100β, NSE, UCHL1, BDNF, E-selectin, and IL-6
timeFrame: Once on the first day of enrollment
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Kirsten M Fiest, PhD
role: PRINCIPAL_INVESTIGATOR
References: