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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Feasibility of Bilateral Central Thalamic FUS Neuromodulation [Time frame: 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 [Time frame: 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 (6)

• Change in Behavioral Responsiveness (Coma Recovery Scale-Revised, CRS-R) [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.]
• Change in Resting-State Functional Connectivity (rs-fMRI) [Time frame: Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.]
• Change in Task-Based Functional Connectivity [Time frame: Assessed at Baseline, 2 weeks after each treatment and 1 year follow-up.]

Eligibility criteria

Inclusion criteria

• Diagnosis of severe traumatic brain injury, hypoxic-ischemic brain injury, or other acute brain injury.
• Glasgow coma scale below 13 when off sedation, or on minimal sedation.
• Absence of another better explanation for the depressed level of consciousness (e.g,, metabolic abnormality, seizures)
• 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).
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre — Toronto

Identifiers

NCT: NCT07694258 · 6798

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗