Clinical trial NCT06426615: Connectivity and Neural Signatures of Consciousness in Unresponsive States
Official title: Connectivity and Neural Signatures of Consciousness In Unresponsive States (CONSCIUS) - a Study of Brain Activity in Disorders of Consciousness
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Brain Injury
Traumatic Brain Injury
Consciousness Disorders
Seizures
Keywords: Consciousness
Seizures
Neural dynamics
Intracranial recordings and stimulation
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Research Foundation Flanders
First posted: 2024-05-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective inclusion of patients implanted with intracranial electrodes.
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: 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...)

Primary outcomes:
measure: Incidence of electrographic epileptiform activity (ictal and ictal-interictal continuum activity) on intracranial versus scalp electroencephalography (EEG).
timeFrame: A maximum of 4 weeks after electrode implantation.
Secondary outcomes:
measure: Correlating neural activity patterns (local field potentials and complexity) with behavioral responsiveness (measured using the Coma Recovery Scale-Revised).
timeFrame: A maximum of 4 weeks after electrode implantation.
measure: Acute effects of electrical stimulation on behavioral responsiveness (measured using the Coma Recovery Scale-Revised).
timeFrame: During electrical stimulation trials, performed in the first 4 weeks after electrode implantation.
measure: Correlation of neural activity profiles with long-term outcome (Coma Recovery Scale-Revised and Glasgow Outcome Scale-Extended)
timeFrame: At 6 months and 1 year follow-up.
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZLeuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Tom Theys, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: