Neuroinflammation During ICU-associated Delirium in Critically Ill Patients and Its Association With Structural and Functional Brain Alterations: a Nested Case-control Study

• Conditions: Critical Illness; Delirium

• Registration Number: NCT04078503
• Lead Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brief Summary

With the present study, the authors aim to improve the knowledge of the pathophysiology of ICU-related delirium. In particular, the authors would like to clarify the possible correlation between neuroinflammation, evaluated longitudinally by serum dosage of 20 different neuroinflammation biomarkers, and brain structural and functional alterations (using brain fMRI).

Detailed Description

Pathophysiology of delirium is poorly understood; neuroinflammation and brain network disruption are claimed as possible causes of delirium.

The authors want to clarify the role of the alterations of different cellular components of neuroinflammation (neurons, glial cells, and endothelium) in delirium development. Moreover, the authors want to understand whether the neuroinflammation process could cause permanent structural and functional brain damage.

In a nested cross-sectional longitudinal case-control observational study in ICU admitted patients.

The objectives of the studies are as follow: 1) Neuroinflammation biomarkers evaluation in non-neurological ICU patients who develop delirium during ICU-stay (case) compared to matched non-delirious ICU patients (control), and 2) their correlation with brain structural and functional alterations evaluated with a resting-state fMRI protocol and PET.

Study Timeline

• Study Start: 2019-03-25
• Study First Submitted: 2019-03-30
• Status Verified: 2019-09
• Study First Submitted QC: 2019-09-01
• Last Update Submitted: 2019-09-01
• Study First Posted: 2019-09-06
• Last Update Posted: 2019-09-06
• Primary Completion: 2021-03-25
• Study Completion: 2021-06-25

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age>18
• All patients admitted that would be expected to stay in ICU for at least 3 days

Exclusion Criteria

• Acute neurological condition
• Chronic neurological condition (i.e., seizures, stroke, muscular illness).
• Hematological malignancy or immunological disease.
• Blood transfusion in the last 2 weeks
• Ongoing sedation
• Any condition which contraindicates MRI execution (presence of non-compatible devices or hemodynamic or respiratory instability).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Serum Neuroinflammation biomarkers in patients developing delirium.	15 days	Comparison of neuroinflammation biomarkers in patients developing delirium vs patients who do not develop delirium.

Secondary Outcome Measures

Name	Time	Method
Correlation between biomarkers alterations and fMRI alterations	15 days	Evaluation of the correlation between serum neuroinflammation biomarkers alteration during delirium development and the alterations noted in during resting state fMRI
fMRI alteration	6 months	Evaluation of brain functional alterations during delirium development (evaluated through resting state fMRI).

Trial Locations

Locations (1)

Spedali Civili di Brescia; 🇮🇹 Brescia, Italy