Window On the Brain

NCT06693492 | Recruiting DMC

• 1 other identifier: PNRR-MAD-2022-12375863
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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.

Conditions

Disorders of Consciousness

Keywords

disorders of consciousness; ultrasound; neuromodulation; minimally conscious state; vegetative state; unresponsive wakefulness syndrome

Outcome Measures

Primary Outcomes (1)

• Brain ultrasonography measures

  These data are based on ultrasound parameters extracted from the ultrasound assessment protocol

  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 (5)

• Level of Consciousness

  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)

• Coma-to-Community outcome measures

  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)

• Coma-to-Community outcome measures

  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)

• Neuroendocrine, inflammatory, and nutritional markers derived from a blood sample

  T0 (time of enrolment)

• EEG connectivity measures

  T0 (time of enrolment)

Study Arms (2)

Chronic patients (DOC duration >=1 year)

EXPERIMENTAL

* Assessment with US technique to characterized the pathophysiological features of chronic DOC * For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention: Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Post-acute patients (DOC duration <1 year)

EXPERIMENTAL

* Assessment with US technique to characterized the pathophysiological features of post-acute DOC and explore its predictive value for chronicization * For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention: Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices

Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention

Interventions

Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention DEVICE

Both chronic and post-acute patients are evaluated through the ultrasound technique to further characterize the mechanisms underlying DOC following acquired brain injuries (e.g., stroke, traumatic brain injury, anoxic events). Furthermore, the predictive value of structural and functional markers for DOC chronicization is explored by following up post-acute DOC patients 1 year after the acute event. Finally, to innovate the therapeutic approach to DOC patients, we adopt the low-intensity focused ultrasound (FUS) on a group of selected 10 patients out of the 100 DOC patients enrolled in the study to modulate brain networks' functioning targeting key brain structures for the recovery of consciousness.

Chronic patients (DOC duration >=1 year); Post-acute patients (DOC duration <1 year)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• previous psychiatric, neurological, or drug abuse history;
• on-going mechanical ventilation.
• From the population enrolled for aim 1, we plan to select ten patients
• \<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.

Sponsors & Collaborators

• IRCCS Istituto delle Scienze Neurologiche di Bologna: collaborator
• S.Anna Rehabilitation Institute: collaborator
• IRCCS Centro Neurolesi Bonino Pulejo: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (4)

Istituto S. Anna, Semi-Intensive Rehabilitation Unit for Acquired Brain Injury

Crotone, Calabria, 88900, Italy

RECRUITING

IRCCS Istituto delle Scienze Neurologiche di Bologna, UO di Medicina Riabilitativa e Neuroriabilitazione

Bologna, Emilia-Romagna, 40139, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico C. Besta, Neurology, Public Helath, Disability Unit

Milan, Lombardy, 20133, Italy

RECRUITING

IRCCS Centro Neurolesi Bonino Pulejo, Neuroimaging Lab

Messina, Sicily, 98124, Italy

RECRUITING

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State

Interventions

Ultrasonography; Diagnosis; Methods

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Investigative Techniques

Central Study Contacts

Matilde Leonardi, MD

CONTACT

+39022394; matilde.leonardi@istituto-besta.it

Francesco Ugo Prada, MD

CONTACT

+39022394; francesco.prada@istituto-besta.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Longitudinal prospective cohort study with baseline and follow-up assessment

Study Record Dates

• First Submitted: December 21, 2023
• First Posted: November 18, 2024
• Study Start: May 20, 2023
• Primary Completion (Estimated): May 19, 2026
• Study Completion (Estimated): May 19, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

IT (4)