Connectivity and Neural Signatures of Consciousness in Unresponsive States

Traumatic Brain Injury Clinical Trial

— CONSCIUS  

Official title:

Connectivity and Neural Signatures of Consciousness In Unresponsive States (CONSCIUS) - a Study of Brain Activity in Disorders of Consciousness

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06426615
• Other study ID #: s67062
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: March 2024
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Steven Smeijers, MD
• Phone: +32 16 34 48 00
• Email: steven.smeijers[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The CONSCIUS study is a prospective, interventional study including patients with acute brain injury and impaired consciousness implanted with intracranial electrodes. The aim of the study is to investigate seizures and thalamocortical neural dynamics underlying behavioral unresponsiveness.

Description:

Individuals with severe brain injury often require extensive treatment in intensive care units (ICU) and hospitalization wards while uncertainty prevails about the recovery of consciousness and cognitive abilities. Especially in the acute phase after injury, treatment decisions have a tremendous impact on outcome, but rely on assessments of behavioral responsiveness which are known to be unreliable and subject to many confounders. Objective, quantifiable diagnostic and prognostic measures that can be deployed at the bedside during the ICU stay are lacking. Development of new metrics are hampered by our lack of a fundamental understanding of (i) thalamocortical network mechanisms underlying consciousness and (ii) brain-injury induced neural dynamics impacting both consciousness and outcome. Continuous EEG monitoring has been used to aid in this respect to (i) predict recovery of consciousness and outcome, and (ii) diagnose nonconvulsive seizures in unresponsive patients. Although promising, it lacks sensitivity, spatial resolution, and causal power. There is an urgent need for techniques allowing high-precision detection of pathological dynamics, patient stratification and prediction of a capacity for consciousness recovery in acute unresponsive patients with brain injury. Intracranial electrodes as part of multimodal monitoring in subjects with impaired consciousness and severe brain injury allow continuous bedside recordings of high spatiotemporal resolution in different network nodes and allows inducing brain perturbations, transcending correlational evidence of network analysis. This technique could increase the detection and treatment of nonconvulsive seizures contributing to brain injury and unresponsiveness and simultaneously allows to study networks supporting consciousness. This can lead to new diagnostic and prognostic biomarkers for recovery based on thalamocortical profiles of activity, reactivity (complexity) and connectivity, ultimately paving to way for the development of biomarker-driven treatments to support early recovery such as deep brain stimulation. Eventually this can contribute to clinical decision making: abstaining from aggressive treatment in patients with no potential for recovery, and more importantly, continuing treatment in subjects with a responsive brain but without clear behavioural correlate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years old or older

• Brain injury of any kind, with impaired consciousness or suspected seizures

Exclusion Criteria:

• < 18 years old

• Known pregnancy

• Any condition that, in the judgement of the investigator, makes participation in the study unsafe or unfeasible (e.g., irreversible coagulopathy, large intracranial tumors, surgical technical problems…)

Related Conditions & MeSH terms

• Acute Brain Injury
• Brain Injuries
• Brain Injuries, Traumatic
• Consciousness Disorders
• Seizures
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Device:
• Intracranial electrodes
Placement of intracranial electrodes in the cortico-subcortical system

Locations

Country	Name	City	State
Belgium	UZLeuven	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	Research Foundation Flanders

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of electrographic epileptiform activity (ictal and ictal-interictal continuum activity) on intracranial versus scalp electroencephalography (EEG).	The primary aim is to compare the incidence of ictal and ictal-interictal continuum epileptiform activity on intracranial versus scalp EEG.	A maximum of 4 weeks after electrode implantation.
Secondary	Correlating neural activity patterns (local field potentials and complexity) with behavioral responsiveness (measured using the Coma Recovery Scale-Revised).	Correlation of profiles of neural activity and reactivity with the behavioral state using the Coma Recovery Scale-Revised (CRS-R).	A maximum of 4 weeks after electrode implantation.
Secondary	Acute effects of electrical stimulation on behavioral responsiveness (measured using the Coma Recovery Scale-Revised).	Effects of electrical stimulation on behavioral responsiveness will be measured using the Coma Recovery Scale Revised (CRS-R).	During electrical stimulation trials, performed in the first 4 weeks after electrode implantation.
Secondary	Correlation of neural activity profiles with long-term outcome (Coma Recovery Scale-Revised and Glasgow Outcome Scale-Extended)	Profiles of activity and reactivity identified during the acute stage of the disease will be correlated with long-term outcome measures mainly at 6m and 1y, using Coma Recovery Scale-Revised and Glasgow Outcome Scale-Extended.	At 6 months and 1 year follow-up.