Connectivity and Neural Signatures of Consciousness in Unresponsive States (CONSCIUS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Seizures; Traumatic Brain Injury; Consciousness Disorders; Acute Brain Injury
• Intervention / Treatment: Device: Intracranial electrodes

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Steven Smeijers, MD; Phone Number: +32 16 34 48 00; Email: steven.smeijers@uzleuven.be
• Study Contact Backup: Name: Tom Theys, MD PhD; Phone Number: +32 16 34 48 00; Email: tom.theys@uzleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZLeuven
      • Contact: Steven Smeijers, MD; Email: steven.smeijers@uzleuven.be
      • Contact: Tom Theys, MD PhD; Email: tom.theys@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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…)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute brain injury; Patients with acute brain injury with reduced consciousness that undergo multimodal intracranial monitoring, or with suspected seizures	Device: Intracranial electrodes; Placement of intracranial electrodes in the cortico-subcortical system; Other Names: Depth electrodes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Research Foundation Flanders
• Investigators: Principal Investigator: Tom Theys, MD PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 29, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Seizures; Consciousness; Neural dynamics; Intracranial recordings and stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Seizures; Consciousness Disorders
• Other Study ID Numbers: s67062

Drug and device information, study documents

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