Consciousness DisorderstFUSNCT06939348
Ultrasound Stimulation for Patients in a Disorder of Consciousness
A study testing The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain. in people with Consciousness Disorders and Disorders of Consciousness Due to Severe Brain Injury, run by University of California, Los Angeles at 4 sites in United States.
Trial 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 multicenter project aims to (1) establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as… Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Consciousness Disorders, Disorders of Consciousness Due to Severe Brain Injury
- What is being tested?
- The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 4 sitesUnited States
- Study dates
- 26 Apr 2025to 29 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of DoC, following international guidelines, as assessed with the CRS-R.
- Prolonged status (>28days post-injury)
- If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and the patient will be willing to remain on a stable regimen during the protocol.
- legally authorized representative available to consent for the patient to participate in the study
Who cannot join
- History of neurological disorder (other than the brain injury).
- Metal implant or other condition precluding safe entry in the MR-environment.
- Manifest continuous spontaneous movement (which would prevent safe/successful imaging).
- Participation in another concurrent clinical trial.
- Need for mechanical ventilation.
- Craniotomy (no bone flap).
- Cranioplasty spanning the left temporal bone window.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Massachusetts General Hospital (The General Hospital Corp.)
Boston, Massachusetts, 02114
Michael Young, MD, 617-724-9247, michael.young@mgh.harvard.edu
Michael Young, MD
- Not yet recruiting
Spaulding Rehabilitation Hospital Corporation, Inc.
Charlestown, Massachusetts, 02129-3109
Jason Lew, DO, 617-724-9247
Jason Lew, DO
- Recruiting
The Regents of the University of California, Los Angeles
Los Angeles, California, 90095
Martin Monti, PhD, 310-825-8546, monti@psych.ucla.edu
Martin Monti, PhD
- Recruiting
Casa Colina Hospital and Centers for Healthcare
Pomona, California, 91767
Jeanette Gumarang, MSN, 9095967733 ext. 2283, jgumarang@casacolina.org
Caroline Schnakers, PhD, 9095967733 ext. 3038, cschnakers@casacolina.org
About this study
Official title: Safety and Efficacy of Thalamic Focused Ultrasound Stimulation (tFUS) for Promoting Recovery After Severe Traumatic Brain Injury
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 multicenter project aims to (1) establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment, (2) establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients and (3) explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
Read the detailed description
Aim 1 - Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment. Investigators will use a multicenter sham-controlled randomized double-blind design to test the efficacy of tFUS for the recovery of consciousness in prolonged DoC, secondary to TBI. Specifically, The investigators will use a sham that is identical to a previous procedure (NCT04921683), except the gel pad used to couple the transducer to the patient's head is "non-transmitting" (as opposed to "transmitting"), thus preventing any penetration of ultrasound inside the head. Approach overview: 40 patients in a prolonged DoC due to TBI (> 28days post injury) will be randomized into one of two conditions: (a) the tFUS-tFUS group will receive 2 sessions of tFUS and (b) the Sham-tFUS group will receive sham sonication in the first session and tFUS in the second session. Measurements: Outcome measures collected prior to tFUS/sham sessions will be compared to outcome measures obtained one week after tFUS/sham sessions. The investigators will assess two endpoint measures: one DoC-specific (i.e., the Coma Recovery Scale Revised - CRS-R; primary measure) [17] (Aim 1a) and one specific to TBI functional outcome (i.e., the Disability Rating Scale; secondary measure) [18] (Aim 1b). Hypotheses Compared to the sham condition, tFUS will lead to a statistically significant increase in consciousness recovery (Aim 1a) and in functional recovery (Aim 1b).
Aim 2 - Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients. Approach overview: The investigators will assess and compare safety and efficacy data in both conditions (ie, the tFUS-tFUS group who will receive 2 tFUS sessions and the Sham-tFUS group who will receive one tFUS session). Measurements: Safety. Proportion of (severe) adverse events (primary measure) will be documented using the Adverse Event Questionnaire (AEQ, also used in NCT04921683) and the Vital signs Care Report Form (CRF) (Common Data Element F0026), [6] within one week of intervention/sham, in the tFUS-tFUS group and in the Sham-tFUS group (Aim 2a); Efficacy. Changes will be assessed, one week after intervention/sham, in the tFUS-tFUS group as compared to the Sham-tFUS group using the CRS-R (secondary measure) (Aim 2b). Hypotheses: Aim 2a: Applying 2 sessions of tFUS will not lead to (higher proportion of) adverse events; Aim 2b: A statistically significant increase in consciousness recovery will be observed when applying two versus one tFUS sessions.
Aim 3 - Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication. The investigators will assess pre-post intervention-related changes in brain activity using electrophysiology in both conditions (i.e., tFUS-tFUS group vs. Sham-tFUS group) (Aim 3a). The investigators will also assess whether the effects of tFUS are TBI-specific by comparing the efficacy observed in our TBI group vs. a non-TBI group (Aim 3b). Approach overview: In addition to our two endpoint measures (i.e., DRS and CRS-R), a 15-minute resting electroencephalogram (EEG) will be collected immediately before and after each tFUS or sham session (Aim 3a). Efficacy (as described in Aim 1a) will be additionally tested in 20 patients in a prolonged DoC due to non-TBI causes (> 28days post injury due to stroke or anoxia) to help determine if tFUS is a TBI specific treatment (Aim 3b). Measurements: For Aim 3a, using the EEG recordings, power spectral density will be calculated within predefined frequency band and ABCD level classification (that reflects the degree of thalamocortical disconnection; primary measure) [7] will be applied based on spectral peaks in these frequencies. For Aim 3b, TBI specific efficacy will be tested based on the change observed one week after tFUS sessions as compared to sham sessions using the CRS-R (secondary measure) in both TBI and non-TBI groups. Hypothesis: Aim 3a: tFUS, but not sham will promote recovery of thalamocortical integrity as estimated by the ABCD level classification based on the Mesocircuit theory [2]; Aim 3b: Compared to sham, tFUS will lead to a statistically significant increase in consciousness recovery, particularly, in the TBI group vs. the non-TBI group.
- Being tested
- The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.
- 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
- Medical subject headings
- Consciousness Disorders, Persistent Vegetative State, Brain Injuries, Traumatic, Stroke, Hypoxia, Brain, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.Device
The BX Pulsar 1002 consists of two main elements: the transducer and the ultrasound console. The transducer itself and the housing for it went through several iterations in order to be compatible with an MRI environment. Currently, the transducer and its housing are deemed MR-conditional at 3T with SAR ≤ 2W/kg. The design includes a solid acoustic coupling gel pad attached to the front of the transducer to provide good acoustic transmission into the scalp. An outer housing was designed to attach the transducer firmly to the head above the temporal window, and to allow it to be moved side to side to accurately target intended structures.
| Study group | Role | What they receive |
|---|---|---|
| Sham-tFUS group | Sham comparator | Sham-tFUS group will receive sham sonication in the first session and tFUS in the second session Receives: Device: The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain. |
| tFUS-tFUS group | Active comparator | tFUS-tFUS group will receive 2 sessions of tFUS Receives: Device: The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment.
Outcome measures collected prior to tFUS/sham sessions will be compared to outcome measures obtained one week after tFUS/sham sessions. The two endpoint measures used will be one DoC-specific measure: the Coma Recovery Scale Revised (CRS-R). The Coma Recovery Scale Revised (CRS-R) ranges from 0 to 23 points, with higher scores indicating better neurological function and level of consciousness. A score of 0 represents the lowest level of neurological functioning, while a score of 23 represents the highest level of neurological functioning.
Measured: From Day 1 to 16
Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients.
Safety. Proportion of (severe) adverse events (primary measure) will be documented using the Adverse Event Questionnaire (AEQ, also used in NCT04921683) and the Vital signs CRF (F0026),22 within one week of intervention/sham, in the tFUS-tFUS group and in the Sham-tFUS group
Measured: From Day 1 to 16
Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
using the EEG recordings, power spectral density will be calculated within predefined frequency band and ABCD level classification (that reflects the degree of thalamocortical disconnection; primary measure) will be applied based on spectral peaks in these frequencies. This measure is calculated in percentage (%) of total power density.
Measured: From Day 1 to 16
Secondary outcomes (3)
Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment
Outcome measures collected prior to tFUS/sham sessions will be compared to outcome measures obtained one week after tFUS/sham sessions. The two endpoint measures used will be one specific to TBI functional outcome: the Disability Rating Scale (DRS). The Disability Rating Scale (DRS) ranges from 0 to 30 points, with higher scores indicating more severe disability. A score of 0 represents no disability, while a score of 30 represents extreme vegetative state or death.
Measured: From Day 1 to 16
Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients.
Efficacy. Changes will be assessed, one week after intervention/sham, in the tFUS-tFUS group as compared to the Sham-tFUS group using the CRS-R. The Coma Recovery Scale Revised (CRS-R) ranges from 0 to 23 points, with higher scores indicating better neurological function and level of consciousness. A score of 0 represents the lowest level of neurological functioning, while a score of 23 represents the highest level of neurological functioning.
Measured: From Day 1 to 16
Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
TBI specific efficacy will be tested based on the change observed one week after tFUS sessions as compared to sham sessions using the CRS-R (secondary measure) in both TBI and non-TBI groups
Measured: From Day 1 to 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2025
- Study start26 Apr 2025
- Primary completion28 Mar 2028 (estimated)
- Study completion29 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Consciousness DisordersStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Sham-controlled 2-arm design. The clinical trial study features a 2-arm, sham-controlled, design. One group will be randomized to receive pulsed thalamic tFUS. The second group will undergo sham procedure. The sham procedure is identical to previous tFUS procedure (NCT04921683), except the gel pad used to couple the transducer to the patient's head is "non-transmitting" (as opposed to "transmitting"), thus preventing any penetration of ultrasound inside the head.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Casa Colina Hospital and Centers for Healthcare, Spaulding Rehabilitation Hospital, Massachusetts General Hospital
- Responsible party
- Principal investigator, Martin M Monti, University of California, Los Angeles
- Investigators
- Martin M Monti, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06939348
- Sponsor's protocol ID
- IRB-24-1241
- Other IDs
- TP230324
- Acronym
- tFUS
- Status last verified
- May 2026
- First submitted
- 7 Apr 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Lutkenhoff ES, Chiang J, Tshibanda L, Kamau E, Kirsch M, Pickard JD, Laureys S, Owen AM, Monti MM. Thalamic and extrathalamic mechanisms of consciousness after severe brain injury. Ann Neurol. 2015 Jul;78(1):68-76. doi: 10.1002/ana.24423. Epub 2015 May 4.
PubMed 25893530Sanz LRD, Lejeune N, Blandiaux S, Bonin E, Thibaut A, Stender J, Farber NM, Zafonte RD, Schiff ND, Laureys S, Gosseries O. Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments. Front Neurol. 2019 Mar 19;10:248. doi: 10.3389/fneur.2019.00248. eCollection 2019.
PubMed 30941094Bogner JA, Whiteneck GG, MacDonald J, Juengst SB, Brown AW, Philippus AM, Marwitz JH, Lengenfelder J, Mellick D, Arenth P, Corrigan JD. Test-Retest Reliability of Traumatic Brain Injury Outcome Measures: A Traumatic Brain Injury Model Systems Study. J Head Trauma Rehabil. 2017 Sep/Oct;32(5):E1-E16. doi: 10.1097/HTR.0000000000000291.
PubMed 28195954Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.
PubMed 24574549Kalmar K, Giacino JT. The JFK Coma Recovery Scale--Revised. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):454-60. doi: 10.1080/09602010443000425.
PubMed 16350986Schnakers C, Monti MM. Disorders of consciousness after severe brain injury: therapeutic options. Curr Opin Neurol. 2017 Dec;30(6):573-579. doi: 10.1097/WCO.0000000000000495.
PubMed 28901969Gosseries O, Demertzi A, Ledoux D, Bruno MA, Vanhaudenhuyse A, Thibaut A, Laureys S, Schnakers C. Burnout in healthcare workers managing chronic patients with disorders of consciousness. Brain Inj. 2012;26(12):1493-9. doi: 10.3109/02699052.2012.695426. Epub 2012 Jun 22.
PubMed 22725684Jennett B. Thirty years of the vegetative state: clinical, ethical and legal problems. Prog Brain Res. 2005;150:537-43. doi: 10.1016/S0079-6123(05)50037-2.
PubMed 16186047Monti MM, Laureys S, Owen AM. The vegetative state. BMJ. 2010 Aug 2;341:c3765. doi: 10.1136/bmj.c3765. No abstract available.
PubMed 20679291Monti MM. Cognition in the vegetative state. Annu Rev Clin Psychol. 2012;8:431-54. doi: 10.1146/annurev-clinpsy-032511-143050. Epub 2012 Jan 3.
PubMed 22224835Tufail Y, Yoshihiro A, Pati S, Li MM, Tyler WJ. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc. 2011 Sep 1;6(9):1453-70. doi: 10.1038/nprot.2011.371.
PubMed 21886108Folloni D, Verhagen L, Mars RB, Fouragnan E, Constans C, Aubry JF, Rushworth MFS, Sallet J. Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation. Neuron. 2019 Mar 20;101(6):1109-1116.e5. doi: 10.1016/j.neuron.2019.01.019. Epub 2019 Feb 11.
PubMed 30765166Yoo SS, Kim H, Min BK, Franck E, Park S. Transcranial focused ultrasound to the thalamus alters anesthesia time in rats. Neuroreport. 2011 Oct 26;22(15):783-7. doi: 10.1097/WNR.0b013e32834b2957.
PubMed 21876461Deffieux T, Younan Y, Wattiez N, Tanter M, Pouget P, Aubry JF. Low-intensity focused ultrasound modulates monkey visuomotor behavior. Curr Biol. 2013 Dec 2;23(23):2430-3. doi: 10.1016/j.cub.2013.10.029. Epub 2013 Nov 14.
PubMed 24239121Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci. 2014 Feb;17(2):322-9. doi: 10.1038/nn.3620. Epub 2014 Jan 12.
PubMed 24413698
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Thalamic Focused Ultrasound Stimulation (tFUS) for Promoting Recovery After Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT06939348
- Acronym / sponsor ID
- tFUS / IRB-24-1241
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Casa Colina Hospital and Centers for Healthcare, Spaulding Rehabilitation Hospital, Massachusetts General Hospital
- Study start
- 26 Apr 2025 (actual)
- Primary completion
- 28 Mar 2028 (estimated)
- Study completion
- 29 Sep 2028 (estimated)
- First posted
- 22 Apr 2025 (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.
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 multicenter project aims to (1) establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment, (2) establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients and (3) explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
Detailed description
Aim 1 - Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment. Investigators will use a multicenter sham-controlled randomized double-blind design to test the efficacy of tFUS for the recovery of consciousness in prolonged DoC, secondary to TBI. Specifically, The investigators will use a sham that is identical to a previous procedure (NCT04921683), except the gel pad used to couple the transducer to the patient's head is "non-transmitting" (as opposed to "transmitting"), thus preventing any penetration of ultrasound inside the head. Approach overview: 40 patients in a prolonged DoC due to TBI (> 28days post injury) will be randomized into one of two conditions: (a) the tFUS-tFUS group will receive 2 sessions of tFUS and (b) the Sham-tFUS group will receive sham sonication in the first session and tFUS in the second session. Measurements: Outcome measures collected prior to tFUS/sham sessions will be compared to outcome measures obtained one week after tFUS/sham sessions. The investigators will assess two endpoint measures: one DoC-specific (i.e., the Coma Recovery Scale Revised - CRS-R; primary measure) [17] (Aim 1a) and one specific to TBI functional outcome (i.e., the Disability Rating Scale; secondary measure) [18] (Aim 1b). Hypotheses Compared to the sham condition, tFUS will lead to a statistically significant increase in consciousness recovery (Aim 1a) and in functional recovery (Aim 1b).
Aim 2 - Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients. Approach overview: The investigators will assess and compare safety and efficacy data in both conditions (ie, the tFUS-tFUS group who will receive 2 tFUS sessions and the Sham-tFUS group who will receive one tFUS session). Measurements: Safety. Proportion of (severe) adverse events (primary measure) will be documented using the Adverse Event Questionnaire (AEQ, also used in NCT04921683) and the Vital signs Care Report Form (CRF) (Common Data Element F0026), [6] within one week of intervention/sham, in the tFUS-tFUS group and in the Sham-tFUS group (Aim 2a); Efficacy. Changes will be assessed, one week after intervention/sham, in the tFUS-tFUS group as compared to the Sham-tFUS group using the CRS-R (secondary measure) (Aim 2b). Hypotheses: Aim 2a: Applying 2 sessions of tFUS will not lead to (higher proportion of) adverse events; Aim 2b: A statistically significant increase in consciousness recovery will be observed when applying two versus one tFUS sessions.
Aim 3 - Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication. The investigators will assess pre-post intervention-related changes in brain activity using electrophysiology in both conditions (i.e., tFUS-tFUS group vs. Sham-tFUS group) (Aim 3a). The investigators will also assess whether the effects of tFUS are TBI-specific by comparing the efficacy observed in our TBI group vs. a non-TBI group (Aim 3b). Approach overview: In addition to our two endpoint measures (i.e., DRS and CRS-R), a 15-minute resting electroencephalogram (EEG) will be collected immediately before and after each tFUS or sham session (Aim 3a). Efficacy (as described in Aim 1a) will be additionally tested in 20 patients in a prolonged DoC due to non-TBI causes (> 28days post injury due to stroke or anoxia) to help determine if tFUS is a TBI specific treatment (Aim 3b). Measurements: For Aim 3a, using the EEG recordings, power spectral density will be calculated within predefined frequency band and ABCD level classification (that reflects the degree of thalamocortical disconnection; primary measure) [7] will be applied based on spectral peaks in these frequencies. For Aim 3b, TBI specific efficacy will be tested based on the change observed one week after tFUS sessions as compared to sham sessions using the CRS-R (secondary measure) in both TBI and non-TBI groups. Hypothesis: Aim 3a: tFUS, but not sham will promote recovery of thalamocortical integrity as estimated by the ABCD level classification based on the Mesocircuit theory [2]; Aim 3b: Compared to sham, tFUS will lead to a statistically significant increase in consciousness recovery, particularly, in the TBI group vs. the non-TBI group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Sham-controlled 2-arm design. The clinical trial study features a 2-arm, sham-controlled, design. One group will be randomized to receive pulsed thalamic tFUS. The second group will undergo sham procedure. The sham procedure is identical to previous tFUS procedure (NCT04921683), except the gel pad used to couple the transducer to the patient's head is "non-transmitting" (as opposed to "transmitting"), thus preventing any penetration of ultrasound inside the head.
| Arm | Type | Receives |
|---|---|---|
| Sham-tFUS group | Sham comparator | Device: The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.Sham-tFUS group will receive sham sonication in the first session and tFUS in the second session |
| tFUS-tFUS group | Active comparator | Device: The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.tFUS-tFUS group will receive 2 sessions of tFUS |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of DoC, following international guidelines, as assessed with the CRS-R.
- Prolonged status (>28days post-injury)
- If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and the patient will be willing to remain on a stable regimen during the protocol.
- legally authorized representative available to consent for the patient to participate in the study
Key exclusion criteria (7 listed)
- History of neurological disorder (other than the brain injury).
- Metal implant or other condition precluding safe entry in the MR-environment.
- Manifest continuous spontaneous movement (which would prevent safe/successful imaging).
- Participation in another concurrent clinical trial.
- Need for mechanical ventilation.
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 |
|---|---|---|
| The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.The BX Pulsar 1002 consists of two main elements: the transducer and the ultrasound console. The transducer itself and the housing for it went through several iterations in order to be compatible with an MRI environment. Currently, the transducer and its housing are deemed MR-conditional at 3T with SAR ≤ 2W/kg. The design includes a solid acoustic coupling gel pad attached to the front of the transducer to provide good acoustic transmission into the scalp. An outer housing was designed to attach the transducer firmly to the head above the temporal window, and to allow it to be moved side to side to accurately target intended structures. | Device | Sham-tFUS group, tFUS-tFUS group |
Primary outcome
Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment.
Time frame: From Day 1 to 16
Outcome measures collected prior to tFUS/sham sessions will be compared to outcome measures obtained one week after tFUS/sham sessions. The two endpoint measures used will be one DoC-specific measure: the Coma Recovery Scale Revised (CRS-R). The Coma Recovery Scale Revised (CRS-R) ranges from 0 to 23 points, with higher scores indicating better neurological function and level of consciousness. A score of 0 represents the lowest level of neurological functioning, while a score of 23 represents the highest level of neurological functioning.
Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients.
Time frame: From Day 1 to 16
Safety. Proportion of (severe) adverse events (primary measure) will be documented using the Adverse Event Questionnaire (AEQ, also used in NCT04921683) and the Vital signs CRF (F0026),22 within one week of intervention/sham, in the tFUS-tFUS group and in the Sham-tFUS group
Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
Time frame: From Day 1 to 16
using the EEG recordings, power spectral density will be calculated within predefined frequency band and ABCD level classification (that reflects the degree of thalamocortical disconnection; primary measure) will be applied based on spectral peaks in these frequencies. This measure is calculated in percentage (%) of total power density.
3 secondary outcomes
Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment
Time frame: From Day 1 to 16
Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients.
Time frame: From Day 1 to 16
Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.
Time frame: From Day 1 to 16
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Background: PubMed 25893530Lutkenhoff ES, Chiang J, Tshibanda L, Kamau E, Kirsch M, Pickard JD, Laureys S, Owen AM, Monti MM. Thalamic and extrathalamic mechanisms of consciousness after severe brain injury. Ann Neurol. 2015 Jul;78(1):68-76. doi: 10.1002/ana.24423. Epub 2015 May 4.
- Results publication: PubMed 30941094Sanz LRD, Lejeune N, Blandiaux S, Bonin E, Thibaut A, Stender J, Farber NM, Zafonte RD, Schiff ND, Laureys S, Gosseries O. Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments. Front Neurol. 2019 Mar 19;10:248. doi: 10.3389/fneur.2019.00248. eCollection 2019.
- Results publication: PubMed 28195954Bogner JA, Whiteneck GG, MacDonald J, Juengst SB, Brown AW, Philippus AM, Marwitz JH, Lengenfelder J, Mellick D, Arenth P, Corrigan JD. Test-Retest Reliability of Traumatic Brain Injury Outcome Measures: A Traumatic Brain Injury Model Systems Study. J Head Trauma Rehabil. 2017 Sep/Oct;32(5):E1-E16. doi: 10.1097/HTR.0000000000000291.
- Results publication: PubMed 24574549Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.
- Results publication: PubMed 16350986Kalmar K, Giacino JT. The JFK Coma Recovery Scale--Revised. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):454-60. doi: 10.1080/09602010443000425.
- Results publication: PubMed 28901969Schnakers C, Monti MM. Disorders of consciousness after severe brain injury: therapeutic options. Curr Opin Neurol. 2017 Dec;30(6):573-579. doi: 10.1097/WCO.0000000000000495.
- Results publication: PubMed 22725684Gosseries O, Demertzi A, Ledoux D, Bruno MA, Vanhaudenhuyse A, Thibaut A, Laureys S, Schnakers C. Burnout in healthcare workers managing chronic patients with disorders of consciousness. Brain Inj. 2012;26(12):1493-9. doi: 10.3109/02699052.2012.695426. Epub 2012 Jun 22.
- Results publication: PubMed 16186047Jennett B. Thirty years of the vegetative state: clinical, ethical and legal problems. Prog Brain Res. 2005;150:537-43. doi: 10.1016/S0079-6123(05)50037-2.
- Results publication: PubMed 20679291Monti MM, Laureys S, Owen AM. The vegetative state. BMJ. 2010 Aug 2;341:c3765. doi: 10.1136/bmj.c3765. No abstract available.
- Results publication: PubMed 22224835Monti MM. Cognition in the vegetative state. Annu Rev Clin Psychol. 2012;8:431-54. doi: 10.1146/annurev-clinpsy-032511-143050. Epub 2012 Jan 3.
- Results publication: PubMed 21886108Tufail Y, Yoshihiro A, Pati S, Li MM, Tyler WJ. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc. 2011 Sep 1;6(9):1453-70. doi: 10.1038/nprot.2011.371.
- Results publication: PubMed 30765166Folloni D, Verhagen L, Mars RB, Fouragnan E, Constans C, Aubry JF, Rushworth MFS, Sallet J. Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation. Neuron. 2019 Mar 20;101(6):1109-1116.e5. doi: 10.1016/j.neuron.2019.01.019. Epub 2019 Feb 11.
- 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.
Martin M Monti, PhD principal investigator
University of California, Los Angeles
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain. in people with Consciousness Disorders and Disorders of Consciousness Due to Severe Brain Injury, run by University of California, Los Angeles at 4 sites in United States.
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 4 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 22 May 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 United States. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin M Monti, PhD (310-825-8546, monti@psych.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Establish short-term efficacy of tFUS as a therapeutic to promote recovery in patients with prolonged DoC as compared to sham treatment. (time frame: From Day 1 to 16). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06939348, which also lists 22 linked publications.
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 22 May 2026.