Ultrasound Stimulation for Patients in a Disorder of Consciousness

NCT06939348 | Recruiting DMC FDA Device

• 2 other identifiers: IRB-24-1241TP230324
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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 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.

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 (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 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.

  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

  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.

  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

  From Day 1 to 16

• Establish dose-related safety and efficacy of tFUS as a therapeutic intervention in prolonged DoC patients.

  From Day 1 to 16

• Explore preliminary predictors and biomarkers of susceptibility and response to thalamic sonication.

  From Day 1 to 16

Study Arms (2)

Sham-tFUS group

SHAM COMPARATOR

Sham-tFUS group will receive sham sonication in the first session and tFUS in the second session

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

Device: The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain.

Interventions

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.

Sham-tFUS group; tFUS-tFUS 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:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Casa Colina Hospital and Centers for Healthcare: collaborator
• Spaulding Rehabilitation Hospital: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (4)

The Regents of the University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Casa Colina Hospital and Centers for Healthcare

Pomona, California, 91767, United States

RECRUITING

Massachusetts General Hospital (The General Hospital Corp.)

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Spaulding Rehabilitation Hospital Corporation, Inc.

Charlestown, Massachusetts, 02129-3109, United States

NOT YET RECRUITING

Related Publications (22)

• 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.

  PMID: 25893530 BACKGROUND

• Sanz 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.

  PMID: 30941094 RESULT

• Bogner 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.

  PMID: 28195954 RESULT

• Thibaut 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.

  PMID: 24574549 RESULT

• Kalmar K, Giacino JT. The JFK Coma Recovery Scale--Revised. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):454-60. doi: 10.1080/09602010443000425.

  PMID: 16350986 RESULT

• Schnakers 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.

  PMID: 28901969 RESULT

• Gosseries 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.

  PMID: 22725684 RESULT

• Jennett 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.

  PMID: 16186047 RESULT

• Monti MM, Laureys S, Owen AM. The vegetative state. BMJ. 2010 Aug 2;341:c3765. doi: 10.1136/bmj.c3765. No abstract available.

  PMID: 20679291 RESULT

• Monti 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.

  PMID: 22224835 RESULT

• Tufail 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.

  PMID: 21886108 RESULT

• Folloni 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.

  PMID: 30765166 RESULT

• Yoo 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.

  PMID: 21876461 RESULT

• Deffieux 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.

  PMID: 24239121 RESULT

• Legon 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.

  PMID: 24413698 RESULT

• Bystritsky A, Korb AS, Douglas PK, Cohen MS, Melega WP, Mulgaonkar AP, DeSalles A, Min BK, Yoo SS. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011 Jul;4(3):125-36. doi: 10.1016/j.brs.2011.03.007. Epub 2011 Apr 1.

  PMID: 21777872 RESULT

• Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injury: A First-in-Man Report. Brain Stimul. 2016 Nov-Dec;9(6):940-941. doi: 10.1016/j.brs.2016.07.008. Epub 2016 Jul 22. No abstract available.

  PMID: 27567470 RESULT

• Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Maejima S, Moriya T. Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. Brain Inj. 1990 Oct-Dec;4(4):315-27. doi: 10.3109/02699059009026185.

  PMID: 2252964 RESULT

• Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O'Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007 Aug 2;448(7153):600-3. doi: 10.1038/nature06041.

  PMID: 17671503 RESULT

• Schiff ND. Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci. 2010 Jan;33(1):1-9. doi: 10.1016/j.tins.2009.11.002. Epub 2009 Dec 1.

  PMID: 19954851 RESULT

• Monti MM, Rosenberg M, Finoia P, Kamau E, Pickard JD, Owen AM. Thalamo-frontal connectivity mediates top-down cognitive functions in disorders of consciousness. Neurology. 2015 Jan 13;84(2):167-73. doi: 10.1212/WNL.0000000000001123. Epub 2014 Dec 5.

  PMID: 25480912 RESULT

• Lutkenhoff ES, McArthur DL, Hua X, Thompson PM, Vespa PM, Monti MM. Thalamic atrophy in antero-medial and dorsal nuclei correlates with six-month outcome after severe brain injury. Neuroimage Clin. 2013 Oct 5;3:396-404. doi: 10.1016/j.nicl.2013.09.010. eCollection 2013.

  PMID: 24273723 RESULT

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

Study Officials

• Martin M Monti, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin M Monti, PhD

CONTACT

310-825-8546; monti@psych.ucla.edu

Caroline Schnakers, PhD

CONTACT

(909) 596-7733; cschnakers@casacolina.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 22, 2025
• Study Start: April 26, 2025
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): September 29, 2028
• Last Updated: October 10, 2025

Record last verified: 2025-04

Locations

US (4)