Clinical trial NCT06693492: Window On the Brain
Official title: Window On the Brain: Diagnostic, Therapeutic, and Prognostic Sonication of Patients With Disorders of Consciousness
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Disorders of Consciousness
Keywords: disorders of consciousness
ultrasound
neuromodulation
minimally conscious state
vegetative state
unresponsive wakefulness syndrome
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Sponsor class: OTHER
Collaborators: name: IRCCS Istituto delle Scienze Neurologiche di Bologna
name: S.Anna Rehabilitation Institute
name: IRCCS Centro Neurolesi Bonino Pulejo
First posted: 2024-11-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Longitudinal prospective cohort study with baseline and follow-up assessment
Primary purpose: DIAGNOSTIC

Brief summary: Disorders of consciousness (DOC) diagnosis suffers from the difficulty to measure the level of consciousness due to the variability associated with behavioural assessments and the difficulty in detecting the residual level of consciousness in patients who do not show any behavioural signs during the behavioural assessment. This issue could be overcome by using instrumental tools, that are expensive and not always available in clinical settings. The ultrasound-based techniques could represent a valid low-cost and more feasible alternative to deep the knowledge about physio-pathological mechanisms underlying DOC and their chronicization. These techniques could be tailored to treat acute and chronic DOC patients from a personalised medicine perspective. Improving the knowledge, management and care pathways of DOC patients and finding new therapeutic options would benefit not only patients but also public health systems.

Detailed description: After acquired brain injuries, Disorders of Consciousness (DOC) may occur and persist for up to many years. DOC range from Unresponsive Wakefulness Syndrome (UWS; presence of reflexive behaviours) to the emergence from Minimally Conscious State (eMCS; presenting signs of functional communication and/or object use). A correct diagnosis affects the legal decisions, prognosis, and potential therapeutic and rehabilitative interventions. Although DOC diagnosis relies on behavioural assessment (Coma Recovery Scale-Revised; CRS-R), several studies highlight the importance of instrumental tools (e.g., neuroimaging and electrophysiology) for improving diagnosis and prognosis despite their complexity, high costs, and low availability. The ultrasound techniques can represent a valid alternative, allowing both to acquire bedside structural and functional data with low costs and less invasiveness, and perform stimulation to boost consciousness improvement and/or recovery. However, limited evidence exists to date about the use of ultrasound techniques for clinical characterization of DOC patients, and only one registered trial is exploring the effectiveness of ultrasound stimulation for consciousness recovery in this clinical population. For these reasons, we aim to explore the brain functioning and morphology with direct ultrasound (US) in DOC patients, providing both anatomical and functional information in real-time. Specifically, the measures extracted from US examination might provide data regarding DOC's physiopathology in a bedside and affordable manner. Moreover, although clinical trials with low-intensity ultrasound modulation of subcortical structures and thalamic nuclei are already in progress, targeting is still empirical. Thus, understanding US parameters in DOC could provide the ground to improve deep brain structures' targeting, tailoring low-intensity ultrasound parameters according to patient's specific needs for improving their level of consciousness.

Eligibility criteria: Aim 1

Inclusion criteria:

* an established diagnosis of DOC (UWS or MCS according to the CRS-R criteria and/or a CRS-R total score ≤22) following severe acquired brain injury;
* age\>18 years old;
* written informed consent obtained from each patient's representative.

Exclusion criteria:

* previous psychiatric, neurological, or drug abuse history;
* on-going mechanical ventilation.

From the population enrolled for aim 1, we plan to select ten patients

Inclusion criteria:

* 18\<age\<65 years;
* medical stability over the previous 30 days;
* presence of the following US variables: low brain stiffness, high elasticity, and adequate level of tissue perfusion;
* written informed consent obtained from each patient's representative;
* structural integrity of both thalami as assessed by MRI.

Exclision criteria:

* contraindications to MRI examination;
* presence of decompressive craniectomy or cranioplasty performed within 30 days;
* presence of epileptogenic features on the EEG and/or drug resistant epileptic crisis history;
* presence of severe muscoloskeletal impairments which are likely to interfere with the correct positioning required for the intervention.

Primary outcomes:
measure: Brain ultrasonography measures
timeFrame: T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients)
Secondary outcomes:
measure: Level of Consciousness
timeFrame: T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients)
measure: Coma-to-Community outcome measures
timeFrame: T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients)
measure: Coma-to-Community outcome measures
timeFrame: T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients)
measure: Neuroendocrine, inflammatory, and nutritional markers derived from a blood sample
timeFrame: T0 (time of enrolment)
measure: EEG connectivity measures
timeFrame: T0 (time of enrolment)
Other outcomes:
Locations:
city: Crotone
country: Italy
facility: Istituto S. Anna, Semi-Intensive Rehabilitation Unit for Acquired Brain Injury
state: Calabria
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna, UO di Medicina Riabilitativa e Neuroriabilitazione
state: Emilia Romagna
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta, Neurology, Public Helath, Disability Unit
state: Lombardy
city: Messina
country: Italy
facility: IRCCS Centro Neurolesi Bonino Pulejo, Neuroimaging Lab
state: Sicily
Study officials:
References: