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The BRAIN Intensive Care Unit (ICU) Study: Bringing to Light the Risk Factors (BRAIN-ICU)

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ClinicalTrials.gov Identifier: NCT00392795
Recruitment Status : Active, not recruiting
First Posted : October 26, 2006
Last Update Posted : December 7, 2022
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Wes Ely, Vanderbilt University Medical Center

Brief Summary:
The primary purpose of this proposal will be to identify potentially modifiable risk factors of long-term cognitive impairment (i.e. development of delirium and exposure to sedative and analgesic medications) in ICU patients. The investigators will quantify the independent contribution of these risk factors to the incidence of long-term cognitive impairment, controlling for other established risk factors including age, pre-existing cognitive impairment, and apolipoprotein E (apoE) genotype. Quantifying the contributions of these modifiable risk factors will pave the way for the development of preventive and/or treatment strategies to reduce the incidence, severity and/or duration of long-term cognitive impairment and improve functional recovery for patients with critical illness.

Condition or disease
Delirium Cognition Disorders Dementia

Detailed Description:
Among Intensive Care Unit (ICU) survivors, subsequent cognitive and functional decline are the greatest threats to meaningful recovery. Six small cohorts indicate that an alarming 30% to 80% of the increasingly millions of ICU survivors develop an acquired long-term cognitive impairment (LTCI) functionally equivalent to mild/moderate dementia that may last years. Additionally, major deficits in health-related quality of life (HRQL), functional status, and an "ICU accelerated" frailty are common, especially in the elderly. A leading and potentially modifiable risk factor for these devastating outcomes may be ICU delirium, which is a predictor of higher mortality, higher cost, and poor cognitive function at discharge. Additionally, heavy and prolonged exposure to potent psychoactive medications routinely administered in high doses to ventilated patients may have lasting yet preventable cognitive and functional effects. In this proposal, Aims 1 and 3 will determine whether delirium is an independent risk factor for the incidence, severity, and/or duration of LTCI (Aim 1) and impaired HRQL (Aim 3) in ICU survivors. Likewise, Aims 2 and 4 will determine whether degree of exposure to sedative and analgesic medications in ICU patients is an independent risk factor for the incidence, severity, and/or duration of LTCI (Aim 2) and impaired HRQL (Aim 4). The study will be a prospective cohort study enrolling 800 mechanically ventilated medical and surgical patients from 3 diverse medical centers over a 39 month period with comprehensive follow-up testing at 3 and 12 months after hospital discharge. This study will quantify whether delirium and sedative/analgesic exposure are indeed risk factors for LTCI and HRQL, controlling for other covariates such as age, medical versus surgical ICU admission, pre-existing cognitive impairment, sepsis, and apoE genotype. This will pave the way for the development of preventive and/or treatment strategies to reduce long-term cognitive impairment and improve the functional recovery of older and younger ICU patients for decades to come. Major threats to recovery for ICU survivors are acquired cognitive and functional decline that can last years, especially in older patients. To pave the way for future preventive and interventional strategies, the cohort will determine to what degree delirium and potent sedatives and analgesics are risk factors for long-term cognitive impairment and functional decline following critical illness.

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Study Type : Observational
Actual Enrollment : 826 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: The BRAIN ICU Study: Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors
Study Start Date : January 2007
Actual Primary Completion Date : December 2010
Estimated Study Completion Date : December 2025

Biospecimen Retention:   Samples With DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Medical and Surgical ICUs

Inclusion Criteria:

  • Patients will be included if they are adult, patients in a medical and/or surgical ICU receiving treatment for any of the following: respiratory failure or cardiogenic or septic shock.

Exclusion Criteria:

Patients who meet the inclusion criteria will be excluded if they meet any of the following criteria:

  • Cumulative ICU time >5 days in the past 30 days, not including the current ICU stay, as this might create a state of flux regarding patients' cognitive baseline
  • Severe cognitive or neurodegenerative diseases that prevent a patient from living independently at baseline, including mental illness requiring institutionalization, acquired or congenital mental retardation, known brain lesions, traumatic brain injury, cerebrovascular accidents with resultant moderate to severe cognitive deficits or ADL dependency, Parkinson's disease, Huntington's disease, severe Alzheimer's disease or dementia of any etiology
  • ICU admission post cardiopulmonary resuscitation with suspected anoxic injury
  • An active substance abuse or psychotic disorder, or a recent (within the past 6 months) serious suicidal gesture necessitating hospitalization. This exclusion will enrich follow-up rates by avoiding patients with whom it is particularly challenging to maintain long-term contact
  • Blind, deaf, or unable to speak English, as these conditions would preclude our ability to perform the follow-up evaluation interviews.
  • Overly moribund and not expected to survive for an additional 24 hours and / or withdrawing life support to focus on comfort measures only.
  • Prisoners.
  • Patients who live further than 200 miles from Nashville and who do not regularly visit the Nashville area.
  • Patients who are homeless and have no secondary contact person available. This exclusion will enrich follow-up rates by avoiding patients with whom it is particularly challenging to maintain long-term contact
  • The onset of the current episode of respiratory failure, cardiogenic shock, or septic shock was > 72 hours ago.
  • Patients who have had cardiac bypass surgery within the past 3 months (including the current hospitalization)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392795

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United States, Tennessee
Saint Thomas Hospital
Nashville, Tennessee, United States, 37205
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute on Aging (NIA)
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Principal Investigator: E Wesley Ely, MD, MPH Vanderbilt University/VA TN Valley GRECC
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Wes Ely, Professor of Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00392795    
Other Study ID Numbers: AG072472 01A1
R01AG027472 ( U.S. NIH Grant/Contract )
First Posted: October 26, 2006    Key Record Dates
Last Update Posted: December 7, 2022
Last Verified: December 2022
Keywords provided by Wes Ely, Vanderbilt University Medical Center:
Critical Care
Long-term cognitive impairment
mechanical ventilation
Critical illness
sedatives and analgesics
Additional relevant MeSH terms:
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Cognition Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations