Disorders of ConsciousnessWOBNCT06693492
Window On the Brain
A study testing Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention in people with Disorders of Consciousness, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 4 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Disorders of Consciousness
- What is being tested?
- Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 4 sitesItaly
- Study dates
- 20 May 2023to 19 May 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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;
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- 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.
Who cannot join
- previous psychiatric, neurological, or drug abuse history;
- on-going mechanical ventilation.
- From the population enrolled for aim 1, we plan to select ten patients
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
IRCCS Istituto delle Scienze Neurologiche di Bologna, UO di Medicina Riabilitativa e Neuroriabilitazione
Bologna, Emilia-Romagna, 40139
Istituto S. Anna, Semi-Intensive Rehabilitation Unit for Acquired Brain Injury
Crotone, Calabria, 88900
IRCCS Centro Neurolesi Bonino Pulejo, Neuroimaging Lab
Messina, Sicily, 98124
Fondazione IRCCS Istituto Neurologico C. Besta, Neurology, Public Helath, Disability Unit
Milan, Lombardy, 20133
About this study
Official title: Window On the Brain: Diagnostic, Therapeutic, and Prognostic Sonication of Patients With Disorders of Consciousness
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.
Read the 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.
- Conditions
- Disorders of Consciousness
- Being tested
- Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention
- Keywords
- disorders of consciousness, ultrasound, neuromodulation, minimally conscious state, vegetative state, unresponsive wakefulness syndrome
- Medical subject headings
- Consciousness Disorders, Persistent Vegetative State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for interventionDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain ultrasonography measures
These data are based on ultrasound parameters extracted from the ultrasound assessment protocol
Measured: 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
The level of consciousness is derived from the Coma Recovery Scale-revised administration (scale's total score ranges from 0 to 23 where 0 represents the worst clinical condition, fully unconscious, and 23 the best one, fully conscious)
Measured: 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
This measure is represented by the Glasgow Outcome Scale-Extended (GOSE-E), used to measure the clinical outcome after a brain injury. The score ranges from 1 to 8, where 1 represents the worst outcome (i.e. death) and 8 the best possible outcome (i.e. good recovery).
Measured: 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
This measure is represented by the Disability Rating Scale (DRS). The maximum score a patient can obtain on the DRS is 29, which correlates with the vegetative state/unresponsive wakefulness syndrome. A person without disability would score zero.
Measured: 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
A blood sample will be collected at T0. The rationale is that pituitary dysfunction, chronic inflammation and malnutrition may be associated with a worst outcome and contribute to chronicization.
The following markers will be collected: haemoglobin, complete blood count, total protein, albumine, transferrine, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), cortisol, adrenocorticotropic hormone (ACTH), C-Reactive Protein (PCR), erythrocyte sedimentation rate (ESR), nonfunctioning pituitary tumors (NFT), growth hormone (GH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone and estradiol.
Measured: T0 (time of enrolment)
EEG connectivity measures
Resting state (rs)-EEG will be used to assess and classify patients with DOC. Quantitative EEG measure (Z scored Power Spectral Density, Dominant Frequency peak, and mean Amplitude) wiil be extracted.
Measured: T0 (time of enrolment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2024
- Study start20 May 2023
- Primary completion19 May 2026
- Study completion19 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disorders of ConsciousnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Longitudinal prospective cohort study with baseline and follow-up assessment
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, S.Anna Rehabilitation Institute, IRCCS Centro Neurolesi Bonino Pulejo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06693492
- Sponsor's protocol ID
- PNRR-MAD-2022-12375863
- Acronym
- WOB
- Status last verified
- Feb 2026
- First submitted
- 21 Dec 2023
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window On the Brain: Diagnostic, Therapeutic, and Prognostic Sonication of Patients With Disorders of Consciousness
- ClinicalTrials.gov ID
- NCT06693492
- Acronym / sponsor ID
- WOB / PNRR-MAD-2022-12375863
- Conditions
- Disorders of Consciousness
- Keywords
- disorders of consciousness, ultrasound, neuromodulation, minimally conscious state, vegetative state, unresponsive wakefulness syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, S.Anna Rehabilitation Institute, IRCCS Centro Neurolesi Bonino Pulejo
- Study start
- 20 May 2023 (actual)
- Primary completion
- 19 May 2026 (actual)
- Study completion
- 19 May 2026 (actual)
- First posted
- 18 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Longitudinal prospective cohort study with baseline and follow-up assessment
| Arm | Type | Receives |
|---|---|---|
| Chronic patients (DOC duration >=1 year) | Experimental | Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention* 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 |
| Post-acute patients (DOC duration <1 year) | Experimental | Device: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention* 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 18<age<65 years;
- medical stability over the previous 30 days;
Key exclusion criteria (3 listed)
- previous psychiatric, neurological, or drug abuse history;
- on-going mechanical ventilation.
- From the population enrolled for aim 1, we plan to select ten patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for interventionBoth 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. | Device | Chronic patients (DOC duration >=1 year), Post-acute patients (DOC duration <1 year) |
Primary outcome
Brain ultrasonography measures
Time frame: 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)
These data are based on ultrasound parameters extracted from the ultrasound assessment protocol
5 secondary outcomes
Level of Consciousness
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: T0 (time of enrolment)
EEG connectivity measures
Time frame: T0 (time of enrolment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention in people with Disorders of Consciousness, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain ultrasonography measures (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.