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

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).

Study Overview

• Status: Unknown
• Conditions: Delirium; Critical Illness

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 Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25123
    • Recruiting
    • Spedali Civili di Brescia
    • Contact: Simone Piva; Phone Number: +393332564230 +393332564230; Email: simone.piva@unibs.it
    • Contact: Fabio Turla; Phone Number: +393332564230; Email: fabioturla2@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

We will enroll 30 critically ill patients in the study (case) matched to 30 controls (see sample size calculation).

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case; All patients aspected to stay in ICU for at least 3 days who will develop delirium
Control; All patients aspected to stay in ICU for at least 3 days who will not develop delirium (1:1 matched with the controls with a propensity score method).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Neuroinflammation biomarkers in patients developing delirium.	Comparison of neuroinflammation biomarkers in patients developing delirium vs patients who do not develop delirium.	15 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Collaborators: University of Turin, Italy; Maastricht University; University of Milano Bicocca; Erasme University Hospital; Università degli Studi di Brescia; Mie University; University of Pisa, Italy

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Anticipated): March 25, 2021
• Study Completion (Anticipated): June 25, 2021

Study Registration Dates

• First Submitted: March 30, 2019
• First Submitted That Met QC Criteria: September 1, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 1, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: fMRI; Functional MRI; neuroinflammation; ICU related delirium
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Delirium; Critical Illness
• Other Study ID Numbers: NP3468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The database is in RedCap. We could share all data
• IPD Sharing Time Frame: Already available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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