Assessment of Safety and Feasibility of FUS Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients With Disorders of Consciousness

The main questions this study aims to answer are:

Can low-intensity FUS neuromodulation be safely and feasibly administered to the bilateral central thalamus in patients with disorders of consciousness (DoC)? Does FUS neuromodulation result in short-term improvements in arousal or behavioral responsiveness? Does FUS neuromodulation produce measurable changes in neural activity on EEG and/or fMRI?

Participants will:

Receive two sessions of low-intensity FUS neuromodulation, spaced four weeks apart, plus or minus one week.

Undergo pre- and post-treatment assessments, including planning CT, MRI/fMRI, EEG, and standardized clinical scales such as the Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS).

Be continuously monitored for safety during and after each FUS treatment. Complete follow-up imaging and clinical assessments approximately 2 weeks after each FUS session, 12 weeks after the second treatment, and at 12 months post-injury when clinically feasible.

Study Overview

• Status: Recruiting
• Conditions: Disorders of Consciousness; Disorders of Consciousness Due to Severe Brain Injury
• Intervention / Treatment: Device: Next Generation Dome Helmet (NGDH)

Detailed Description

This is a prospective, single-center, single-arm, open-label pilot clinical trial. Approximately 10-15 participants are expected to be enrolled. Each participant will receive two sessions of low-intensity focused ultrasound (FUS) neuromodulation targeting the bilateral central thalamus, spaced four weeks apart, plus or minus one week. Participants will be followed for safety, clinical, imaging, and neurophysiological assessments, including follow-up through 12 weeks after the second treatment and, when clinically feasible, at 12 months post-injury.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Benjamin Davidson, MD, PhD; Phone Number: 80093 (416) 480-6100; Email: benjamin.davidson@sunnybrook.ca
• Study Contact Backup: Name: Jaana Leppala, Masters of Neuroscience; Phone Number: 6476852284; Email: jaana.leppala@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Benjamin Davidson, MD, PhD; Phone Number: 80093 (416) 480-6100; Email: benjamin.davidson@sunnybrook.ca
      • Contact: Nir Lipsman, MD, PHD, FRCSC, FAANS; Phone Number: (416)-480-6954; Email: Nir.Lipsman@sunnybrook.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of severe traumatic brain injury, hypoxic-ischemic brain injury, or other acute brain injury.
2. Glasgow coma scale below 13 when off sedation, or on minimal sedation.
3. Absence of another better explanation for the depressed level of consciousness (e.g,, metabolic abnormality, seizures)
4. Intracranial pressure (ICP) is within a normal range (< 20 cm H2O), or, a neurosurgeon associated with the study and/or the treating physician agree that ICP is likely < 20 cm H2O based on clinical and neuroimaging information (acknowledging the limitations of non-invasive assessment of ICP53).
5. The treating physician and/or neurosurgeon associated with the study evaluate it to be safe for the patient to be transported to the MRI scanner for a ~45 minute scan.

Exclusion Criteria:

1. Active seizure activity or post-anoxic myoclonus at the time of proposed treatment
2. Taking full anti-coagulation medication (does not include deep-vein-thrombosis chemoprophylaxis)
3. Skull anatomy incompatible with safe FUS delivery (as determined by CT)
4. Medical instability that would preclude safe transport or prolonged supine positioning
5. Presence of any MRI-incompatible implants or devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Focused Ultrasound Neuromodulation; Participants will receive two sessions of MRI-guided low-intensity focused ultrasound (FUS) neuromodulation using the FUS Next Generation Dome Helmet (NGDH), targeting the bilateral centromedian and parafascicular nuclei of the thalamus. Treatments will be spaced four weeks apart, plus or minus one week. All participants will receive the same intervention and will be followed for safety, feasibility, clinical outcomes, and neurophysiological effects, including follow-up through 12 weeks after the second treatment and additional assessments at 12 months post-injury when feasible.

Device: Next Generation Dome Helmet (NGDH); Participants will receive MR-guided focused ultrasound neuromodulation using the Next Generation Dome Helmet (NGDH). Each participant will undergo two treatment sessions spaced four weeks apart. MRI and CT imaging will be used to guide targeting of the bilateral centromedian/parafascicular nuclei of the thalamus. Continuous monitoring will be performed during each session, and follow-up clinical, EEG, and MRI assessments will be conducted to evaluate safety, feasibility, and preliminary effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Bilateral Central Thalamic FUS Neuromodulation	Feasibility will be defined as the proportion of enrolled participants who complete both focused ultrasound (FUS) neuromodulation sessions without protocol deviation or occurrence of a serious adverse event (SAE) related to the procedure.	Assessed at Screening/Baseline, Treatment 1, Mid-treatment assessment (2 weeks after Treatment 1), Treatment 2 (4 weeks after Treatment 1), 2-week follow-up (2 weeks after each treatment), 12 weeks after Treatment 2, and 1-year follow-up.
Safety of FUS Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients with Disorders of Consciousness	Safety will be assessed by the frequency, type, and severity of adverse events (AEs) and serious adverse events (SAEs) following FUS treatment. Events of interest include seizures, autonomic instability, new focal neurological deficits, clinical deterioration, or structural abnormalities detected on post-treatment MRI.	Assessed at Screening/Baseline, Treatment 1, Mid-treatment assessment (2 weeks after Treatment 1), Treatment 2 (4 weeks after Treatment 1), 2-week follow-up (2 weeks after each treatment), 12 weeks after Treatment 2, and 1-year follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Behavioral Responsiveness (Coma Recovery Scale-Revised, CRS-R)	The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment used to measure level of consciousness in patients with disorders of consciousness. The CRS-R consists of 6 subscales (Auditory, Visual, Motor, Oromotor/Verbal, Communication, and Arousal) that evaluate reproducible signs of awareness. Total scores range from 0 to 23, with higher scores indicating greater behavioral responsiveness and higher levels of consciousness.	Assessed at Baseline, Treatment 1, Mid-treatment assessment (2 weeks after Treatment 1), Treatment 2 (4 weeks after Treatment 1), 2-week follow-up (2 weeks after each treatment), 12 weeks after Treatment 2, and 1-year follow-up.
Change in Glasgow Coma Scale (GCS)	The Glasgow Coma Scale (GCS) is a standardized clinical tool used to assess a patient's level of consciousness, particularly after brain injury. It evaluates three components of responsiveness: eye opening, verbal response, and motor response. Each component is scored individually and then summed to produce a total score ranging from 3 to 15. Higher scores indicate better neurological function and greater levels of consciousness, while lower scores reflect more severe impairment.	Assessed at Baseline, Treatment 1, Mid-treatment assessment (2 weeks after Treatment 1), Treatment 2 (4 weeks after Treatment 1), 2-week follow-up (2 weeks after each treatment), 12 weeks after Treatment 2, and 1-year follow-up.
Change in Rancho Los Amigos Scale Level	The Rancho Los Amigos Scale (also known as the Rancho Los Amigos Levels of Cognitive Functioning Scale) is an 8-level clinical scale used to assess cognitive recovery and behavioral responsiveness following severe brain injury. The scale ranges from Level I (No Response) to Level VIII (Purposeful and Appropriate Response). Higher levels indicate greater cognitive functioning, improved awareness, and more appropriate and consistent behavioral responses. Only participants who scored 23 on CRS-R will complete The Rancho Los Amigos Scale.	Assessed at Baseline, Treatment 1, Mid-treatment assessment (2 weeks after Treatment 1), Treatment 2 (4 weeks after Treatment 1), 2-week follow-up (2 weeks after each treatment), 12 weeks after Treatment 2, and 1-year follow-up.
Change in EEG Measures of Neural Activity	Electroencephalography (EEG) will be used to assess changes in neural activity before and after focused ultrasound (FUS) neuromodulation. EEG measures will include spectral power (frequency band power across delta, theta, alpha, beta, and gamma ranges), spectral entropy (a measure of signal complexity and cortical activation), and event-related responses during task-based paradigms (e.g., motor imagery and passive auditory language tasks). Higher spectral entropy and increased task-related cortical responses are generally interpreted as reflecting greater cortical activation and improved network engagement associated with arousal and awareness. Changes in resting-state spectral power and task-evoked responses will be assessed relative to baseline.	Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.
Change in Resting-State Functional Connectivity (rs-fMRI)	Resting-state functional MRI will be used to assess changes in resting-state functional connectivity between the central thalamus and frontal/parietal cortical regions. Connectivity may be quantified using seed-based connectivity metrics and network-level connectivity measures derived from resting-state data. Changes will be assessed relative to baseline.	Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.
Change in Task-Based Functional Connectivity	Task-based functional MRI will be used to assess brain activation and network engagement during structured paradigms, such as motor imagery and passive auditory language tasks. Task-related blood-oxygen-level-dependent (BOLD) responses will be used to assess regional brain activation and network-level engagement. Changes will be assessed relative to baseline.	Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: neuromodulation; focused ultrasound; FUS
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Consciousness Disorders
• Other Study ID Numbers: 6798

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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