Illuminating Neuropsychological Dysfunction and Systemic Inflammatory Mechanisms Gleaned After Hospitalization in Trauma-ICU Study (INSIGHT-ICU)

Cognitive skills are essential to live independently, manage finances, maintain employment, and function in society. Loss of these cognitive skills puts a tremendous burden on society as seen with dementias, Alzheimer's disease, and traumatic brain injury. The INSIGHT-ICU Study (Illuminating Neuropsychological dysfunction and Systemic Inflammatory mechanisms Gleaned after Hospitalization in Trauma-ICU Study) is the first comprehensive and longitudinal long-term cognitive impairment study after traumatic injury. The societal impact of long-term cognitive impairment after trauma is immense given that these patients are young and constitute a large proportion of employable adults.

Study Overview

• Status: Active, not recruiting
• Conditions: Delirium; Critical Illness; Cognitive Impairment; Trauma; Traumatic Brain Injury; ICU; Polytrauma; Alzheimer; Early Onset
• Intervention / Treatment: Other: Non-interventional observational prospective cohort study

Detailed Description

Cognitive skills are the crucial abilities required to manage money, maintain employment, and live independently. Long-term cognitive impairment (LTCI) is a disabling loss of these skills that can persist for months to years. LTCI frequently occurs after primary brain injury (e.g., traumatic brain injury, hypoxia), but older LTCI research has not characterized primary brain injury using NIH Common Data Elements in Imaging, the contributions of polytrauma, and the time-course of the critical illness, including secondary brain injury (i.e., delirium). In our recent large study of ICU patients without primary brain injury, over 50% of patients had LTCI and nearly 50% were newly unemployed at one-year post-discharge. In-hospital delirium was the major independent risk factor for LTCI. Surprisingly, this delirium-related LTCI was similar to the LTCI seen in past studies after moderate traumatic brain injury. Thus, both primary and secondary brain injury are associated with LTCI, yet they have not been studied together. There is an unmet need to define the independent risks of primary brain injury and delirium in LTCI. The trauma ICU patient is at combined risk for primary brain and/or multisystem injuries, secondary brain injury, and critical illness; these critically injured patients are the unique population to address this knowledge gap.

Therefore, our FIRST HYPOTHESIS is that delirium duration is an independent risk for the severity of LTCI, controlling for confounders of co-morbidities, socioeconomic status, pre-injury employment, primary brain injury, polytrauma, and critical illness. AIM 1 will address this hypothesis by defining the independent risks of primary and secondary brain injury on the severity of LTCI among trauma ICU subjects.

But, LTCI's real-world impact on employment has not been explained or adjusted for the above confounders and social factors. Accordingly, our SECOND HYPOTHESIS is that LTCI severity is an independent risk for lower level of employment, adjusting for similar confounders. AIM 2 will delineate the independent risk of LTCI severity on employment among trauma ICU survivors. Lastly, LTCI pathogenesis may be related to persistent inflammation.

So, our THIRD HYPOTHESIS is that hospital discharge biomarkers of persistent inflammation will be independent risks for LTCI severity, adjusting for similar confounders. AIM 3 will explore the mechanistic role of plasma inflammatory biomarkers on LTCI severity among trauma ICU survivors.

• Study Type: Observational
• Enrollment (Actual): 432

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be broadly eligible for inclusion if they are Adult trauma and/or burn patients, injury from any mechanism, requiring admission to an Adult ICU for the treatment of shock (any type), respiratory failure, and/or neurologic failure, including monitoring for deteriorating brain function.

Description

Inclusion Criteria:

• Adult trauma and/or burn patients, injury from any mechanism, requiring admission to an Adult ICU for the treatment of shock (any type), respiratory failure, and/or neurologic failure, including monitoring for deteriorating brain function.

Exclusion Criteria:

• Inability to obtain informed consent within the 72 hours following injury

  • Attending physician refusal
  • Patient and/or surrogate refusal
  • 72-hour period of eligibility was exceeded before the patient was screened
  • Patient unable to consent and no surrogate available within the 72-hour period
• Residence > 200 miles from study site and do not regularly visit the Nashville area.
• Patients who are homeless and have no secondary contact person available.
• Severe prior cognitive or neurodegenerative disorder that prevents a patient from living independently at baseline
• Inability to understand English or Spanish or bilateral deafness or bilateral vision loss
• Inability to co-enroll with other studies
• Prisoners
• Substance abuse requiring treatment, known psychotic disorder (e.g., schizophrenia or schizoaffective disorder), or recent (within the past 6 months) serious suicidal gesture necessitating hospitalization
• Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family or the medical team (e.g., likely to withdraw life support measures within 24 hours of screening).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critically Ill Trauma Patients; Non-intervention observational prospective cohort study	Other: Non-interventional observational prospective cohort study; Non-interventional observational prospective cohort study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LTCI (Long-term Cognitive Impairment) as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	LTCI (Long-term Cognitive Impairment) as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	12 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Mayur B Patel, MD,MPH, Vanderbilt University Medical Center

Publications and helpful links

Helpful Links

• NIH RePORTER

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2017
• Primary Completion (Actual): February 25, 2022
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 21, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Alzheimer's Disease; Neuroinflammation; Cognitive Impairment; ICU; Dementia; Cognition; Critical Illness; Subarachnoid hemorrhage; Neuropsychology; Trauma; Traumatic Brain Injury; Critical Care; Delirium; Injury; Employment; Encephalopathy; Burn; Return to Work; Polytrauma; Neuropsychological Outcomes; Intracerebral hemorrhage; Head Injury; INSIGHT-ICU; INSIGHT; Neurotrauma; Subdural hemorrhage; Neuropsychology Dysfunction; Inflammatory Mechanisms; Critically Injured; Long-term Cognitive Impairment; ICU-related Dementia
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Craniocerebral Trauma; Trauma, Nervous System; Cognition Disorders; Delirium; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Cognitive Dysfunction; Critical Illness; Multiple Trauma
• Other Study ID Numbers: 171335; R01GM120484 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No