Circadian Melatonin Rhythms in Critically Ill Patients With Delirium

ICU Delirium Clinical Trial

Official title:

Circadian Melatonin Rhythms in Critically Ill Patients With Delirium - A Prospective Single-centre Observational Proof-of-concept Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04721613
• Other study ID #: BASEC_01_2021
• Status: Completed
• Start date: March 31, 2021
• Est. completion date: May 25, 2023

Study information

• Verified date: December 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Delirious patients often suffer from sleep disturbances such as insomnia, sleep fragmentation, daytime somnolence, and reversal of sleep-wake rhythms. There is evidence, that patients suffering from hyperactive, as well as hypoactive and mixed delirium suffer from disturbed circadian rhythm. The investigators hypothesize that the circadian melatonin profile in critically ill delirious patients measured at two-hourly intervals deviates significantly in terms of phase, width and amplitude from non-delirious critically ill patients with similar age and SOFA (Sequential Organ Failure Assessment) score.

Description:

Delirium is a highly prevalent neuropsychological condition in patients admitted to the ICU. Occurrence of a delirium in critically ill patients is associated with prolonged ICU stay and longer hospitalization, reduced quality of life and increased mortality. Furthermore, it is accompanied by a higher risk of cognitive disorder after ICU discharge.

Delirium is defined as an acute, usually reversible state of disturbance of consciousness with a change of perception and cognition. Its fluctuating course leads to a division in three subgroups: hyperactive, hypoactive and mixed delirium. Hyperactive delirious patients present agitated and anxious behaviour, hypoactive delirium however is characterised by withdrawal, somnolence and reduced responsiveness to stimuli. The mixed subtype shows alternating characteristics from both hyperactive and hypoactive delirium.

ICU patients especially in the post-operative setting frequently show several risk factors for delirium, including environmental changes, advanced age, alcohol abuse, dementia, demand for vasopressors, increased doses of opioids or metabolic disturbances.

Sleep and many symptoms that occur in delirium are influenced by the circadian timing system and therefore are thought to be closely related. The neurohormone melatonin plays a major role in regulating circadian rhythms. It is produced in the pineal gland and its diurnal secretion pattern is under the control of the central circadian pacemaker located in the suprachiasmatic nuclei of the anterior hypothalamus. Under normal entrained condition melatonin starts to increase one to three hours prior habitual bedtime, which often coincides with the onset of darkness outside. Thus, melatonin is often referred to as the hormone of darkness. Peak melatonin levels occur approximately two hours prior usual rise time (usually between 2 and 5 A.M.). Melatonin levels are lower during daytime independent of experienced light levels.

Delirious patients often suffer from sleep disturbances such as insomnia, sleep fragmentation, daytime somnolence, and reversal of sleep-wake rhythms. There is evidence that hyperactive as well as hypoactive and mixed delirium is connected to disturbed circadian rhythm. This leads to the question whether there is a link between delirium syndromes as well as different delirium subtypes and potential alterations in circadian melatonin plasma levels compared to non-delirious patients.

Plasma melatonin levels can be assessed in saliva, blood and urine. Due to its rapid metabolisation plasma melatonin levels represent a precise proxy of the current pineal secretion. It therefore is reasonable to collect plasma samples for melatonin assessments frequently throughout the study period to obtain an accurate time course of the circadian melatonin rhythm profile.

There is suggestive evidence that regulating melatonin levels during delirium lowers the incidence of delirium and leads to a reduction of duration and severity of the disorder.

The investigators hypothesize that the circadian melatonin profile in critically ill delirious patients measured in two-hourly intervals across 24 hours deviates significantly from non-delirious critically ill patients with similar age and SOFA (Sequential Organ Failure Assessment) score in terms of phase, width and amplitude.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 25, 2023
• Est. primary completion date: May 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients (aged 55 years or older)

2. Admission to the ICU

3. Current delirium (ICDSC =4)

4. Functioning venous or arterial line for blood sample collection

Exclusion Criteria:

1. Delirium prior to ICU admission

2. Intake of beta blockers within 48 hours before study inclusion and during study period

3. Premenopausal women

4. Terminal state

5. Dementia

6. Substance abuse including alcohol in current medical history

Related Conditions & MeSH terms

• Delirium
• ICU Delirium

Intervention

Other:
• Assessment of Melatonin level
Measuring the plasma or serum melatonin in pg/ml during the first 24 hours after delirium diagnosis in two-hour intervals.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Centre for Chronobiology, Transfaculty Research Platform Molecular and Cognitive Neurosciences (MCN), Psychiatric Hospital of the University of Basel (UPK)

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Melatonin profile	Difference in melatonin profile in ICU patients with delirium compared to non-delirious patients	24 hours