Promoting Recovery After Brain Injury Using Focused Ultrasound

NCT07277309 | Recruiting FDA Device

• 2 other identifiers: 2025P0028161K23NS140495
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

The overall aim of this study is to develop an intervention that can help recovery in patients surviving severe brain injury but failing to fully recover. In particular, this project aims to (1) determine neurobehavioral responses to low-intensity focused ultrasound (LIFUP) in patients with disorders of consciousness (DoC) following brain injury, (2) determine neurophysiologic (EEG) responses to LIFUP in patients with DoC and (3) identify and evaluate ethical perspectives of patient representatives (family members and surrogate decision-makers) surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC.

Conditions

Consciousness Disorders; Disorders of Consciousness Due to Severe Brain Injury

Keywords

Disorder of Consciousness; Vegetative State; Minimally Conscious State; Minimally Conscious State Plus; Minimally Conscious State Minus; Traumatic Brain Injury; CVA (Cerebrovascular Accident); Anoxia, Brain; Thalamic Infarction; Coma; Prolonged

Outcome Measures

Primary Outcomes (4)

• Determine neurobehavioral responses to LIFUP in patients with DoC: Coma Recovery Scale - Revised (CRS-R)

  Outcome measures collected prior to LIFUP sessions will be compared to outcome measures obtained after LIFUP sessions. The Coma Recovery Scale Revised (CRS-R) ranges from 0 to 23 points, with higher scores indicating better neurobehavioral function and level of consciousness. The CRS-R consists of 6 subscales designed to assess auditory function, receptive and expressive language, visuoperception, communication ability, motor functions, and arousal level. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best).

  Days 1-3

• Determine neurobehavioral responses to LIFUP in patients with DoC: Disability Rating Scale (DRS)

  Outcome measures collected prior to LIFUP sessions will be compared to outcome measures obtained after LIFUP sessions. The DRS ranges from 0 to 30 points, with higher scores indicating more severe disability. DRS subscale scores include eye opening \[score range 0-3\], communication \[score range 0-4\], motor response \[score range 0-5\], cognitive ability for feeding \[score range 0-3\], cognitive ability for toileting \[score range 0-3\], cognitive ability for grooming \[score range 0-3\], level of function \[score range 0-5\], and employability \[score range 0-3\]. Subscale scores are summed to produce the total score.

  Days 1-3

• Determine neurophysiologic responses to LIFUP in patients with DoC

  Using electroencephalography (EEG) recordings, we will compute power spectral density within predefined frequency bands and derive ABCD-level classifications, resting-state complexity metrics, and responsiveness indices that quantify the degree of thalamocortical disconnection.

  Days 1-3

• Identify and evaluate ethical perspectives of patient representatives surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC

  Family members or surrogate decision-makers (i.e., legally authorized healthcare proxies of study participants with DoC), will be engaged in interviews to capture their expectations, perspectives, and concerns surrounding the use and deployment of neuromodulation techniques in the context of brain injury. The semi-structured interview will center on key themes: hopes and expectations for neuromodulation technology; views on the informed consent process and data privacy related to neural data; considerations of equity in access to neuromodulation therapies; areas of uncertainty or concern regarding risks and benefits; and perceived roles of caregivers and families in the neuromodulation decision-making process. This approach is designed to elicit a nuanced understanding of ethical considerations as viewed by those most impacted, thereby informing a robust ethical framework that aligns research and clinical practices with the values and needs of patients and their families.

  Days 1-3

Secondary Outcomes (1)

• Brain MRI-derived responsiveness index (structural-functional signature predicting LIFUP response)

  Day 1

Study Arms (1)

LIFUP group

EXPERIMENTAL

Participants will receive low-intensity focused ultrasound intervention. Participants are also anticipated to undergo advanced MRI and EEG. Surrogate decision makers (family members) and recovered patients will undergo a semi-structured interview.

Device: Low-intensity focused ultrasound

Interventions

Low-intensity focused ultrasound DEVICE

Low-intensity focused ultrasound pulsations (LIFUP) will be delivered to the brain, along with advanced MRI and EEG. Surrogate decision makers (family members) and recovered patients will undergo a semi-structured interview.

LIFUP group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Brain injury resulting in DoC diagnosis, following international guidelines
• At least 18 years of age
• Legally authorized representative (surrogate) available to consent

You may not qualify if:

• History of neurological disorder other than the brain injury
• Metal implant or other condition precluding MRI
• Manifest continuous spontaneous movement (which would prevent safe/successful MRI)
• Participation in concurrent therapeutic study
• Pregnancy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Massachusetts General Hospital (The General Hospital Corp.)

Boston, Massachusetts, 02114, United States

RECRUITING

Spaulding Rehabilitation Hospital Corporation, Inc.

Cambridge, Massachusetts, 02138, United States

RECRUITING

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State; Brain Injuries, Traumatic; Stroke; Hypoxia, Brain; Coma

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; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory

Central Study Contacts

Michael Young, MD, MPhil

CONTACT

410-808-1196; michael.young@mgh.harvard.edu

Jason Lew, DO

CONTACT

617-724-9247; jlew3@mgb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 11, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-01

Locations

US (2)