Cholinesterase Activity and DeliriUm During Critical Illness Study

NCT03098472 | Completed

• 1 other identifier: CADUCeuS
• Study Type: observational
• Target: 279
• Locations: 1 country
• Sites: 1

Brief Summary

Delirium is a syndrome of acute brain dysfunction involving attention and cognition that affects up to half of older hospitalized patients and 50%-75% of critically ill ICU patients, such that millions of patients worldwide experience this acute threat to their health and well being every year. One-third to half of critical illness survivors struggle with a dementia-like disorder similar in severity to moderate-to-severe traumatic brain injury or Alzheimer's Disease, and the only proven risk factor that is potentially modifiable is delirium in the ICU. Despite the frequency and impact of delirium in the ICU, little is known regarding the biological mechanisms that lead to this form of organ dysfunction during critical illness. A widely held hypothesis proposes that inflammation is regulated by the cholinergic system, and that this interaction plays a pivotal role whether delirium developments in the setting of acute illness. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are enzymes that hydrolyze the neurotransmitter acetylcholine. Changes in the activity of these enzymes, which can be measured in whole blood, reflect altered regulation of circulating acetylcholine. AChE and BuChE activities have promise as both predictors of delirium (when found to be low at admission) and biomarkers of delirium (when low during serial measurement). Neither of these biomarkers, however, have been studied in the ICU setting where delirium risk is the highest. The current investigation, therefore will be the first to determine the validity of circulating AChE and BuChE activities as biomarkers of delirium during critical illness and subsequent cognitive impairment after discharge. This study will measure whole blood AChE and butyrylcholinesterase BuChE activities within the framework of the ICU Delirium and Cognitive Impairment Study Group's ongoing clinical trials in critically ill patients.

Conditions

Delirium; Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Delirium

  Confusion Assessment Method for the ICU

  During hospital stay until death or hospital discharge, whichever comes first, up to 30 days

Secondary Outcomes (1)

• Global cognition

  At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge

Other Outcomes (4)

• Activities of daily living

  At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge

• Instrumental activities of daily living

  At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge

• Quality of life and generic health status

  At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will include all patients in the ICU Delirium and Cognitive Impairment Study Group's ongoing clinical trials over a two-year period of time.

You may not qualify if:

• Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family or the medical team (e.g., likely withdrawal of life support measures within 24 hours of screening)
• Active substance abuse, psychotic disorder, or homelessness without a secondary contact person (which would make long-term follow-up difficult)
• Blindness or deafness (which would prevent assessment of the study's outcomes)
• Inability to obtain informed consent

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• DR. FRANZ KOHLER CHEMIE GMBH: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (1)

• Hughes CG, Boncyk CS, Fedeles B, Pandharipande PP, Chen W, Patel MB, Brummel NE, Jackson JC, Raman R, Ely EW, Girard TD. Association between cholinesterase activity and critical illness brain dysfunction. Crit Care. 2022 Dec 6;26(1):377. doi: 10.1186/s13054-022-04260-1.

  PMID: 36474266 DERIVED

MeSH Terms

Conditions

Delirium; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 31, 2017
• Study Start: May 8, 2017
• Primary Completion: January 1, 2020
• Study Completion: February 1, 2021
• Last Updated: March 11, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)