Ultrasound Stimulation for Disorders of Consciousness

(tFUS Trial)

Recruiting at 3 trial locations

Overseen By Martin M Monti, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Disqualifiers: Neurological disorder, Metal implant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tFUS (transcranial focused ultrasound stimulation), which uses ultrasound waves to aid individuals with severe brain injuries who have not fully regained consciousness. The goal is to determine if tFUS can safely and effectively improve recovery compared to a placebo treatment. Participants will receive either real tFUS or a sham (fake) treatment to assess differences in outcomes. Individuals who have experienced a brain injury and have been unconscious for more than 28 days might be suitable for this study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance recovery options for severe brain injuries.

Will I have to stop taking my current medications?

If you are on a psychotropic medication regimen, you will need to keep it stable for at least 4 weeks before joining the study and remain on a stable regimen during the trial.

What prior data suggests that this ultrasound stimulation technique is safe for patients with disorders of consciousness?

Research has shown that treatments using the Brainsonix BX Pulsar 1002 are generally safe. Studies have found that this device, which uses gentle sound waves aimed at the brain, is well-tolerated. Users did not experience major side effects. Some research even checked for changes in brain function and found nothing concerning.

The device is currently under an Investigational Device Exemption, meaning it is still being tested. However, current findings about its safety are promising. The goal is to ensure the treatment is safe and effective before it becomes more widely available. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of ultrasound stimulation for disorders of consciousness because it offers a non-invasive way to potentially improve brain function in patients with severe brain injuries. Unlike traditional treatments that might rely on medication or surgical interventions, the Brainsonix BX Pulsar 1002 uses focused ultrasound to target specific brain areas, possibly enhancing neural activity and connectivity. This technique is intriguing because it could provide faster and more targeted results without the side effects associated with drugs. Moreover, the potential for tailoring the intensity and location of the ultrasound offers a personalized approach to treatment, which is a significant advancement in this field.

What evidence suggests that the Brainsonix BX Pulsar 1002 is effective for disorders of consciousness?

This trial will compare the effects of ultrasound stimulation using the Brainsonix BX Pulsar 1002 in two different groups. Research has suggested that non-invasive brain stimulation, such as the Brainsonix BX Pulsar 1002, can assist with consciousness disorders. Studies have shown that ultrasound, which uses sound waves, can aid recovery in patients with severe brain injuries who haven't fully healed. It stimulates the brain, potentially activating areas that aren't functioning properly. Initial findings are promising, with some patients responding well to this treatment. While more research is needed, early evidence suggests it could be a helpful option for those in a prolonged state of consciousness disorder. ^{4 6 7 8 9}

Who Is on the Research Team?

Martin M Monti, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for patients with chronic consciousness disorders due to severe brain injury. Participants must have a stable medical condition and be between the ages of 18-75. They should not have any metal in their head, history of seizures, or skin abnormalities at the ultrasound site.

Inclusion Criteria

I have been injured for more than 28 days.

Legally authorized representative available to consent for the patient to participate in the study

My mental health medication has been stable for 4 weeks and I can keep it unchanged during the study.

Exclusion Criteria

I have had brain surgery without removal of the skull bone.

Metal implant or other condition precluding safe entry in the MR-environment

I can't stay still enough for clear imaging tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tFUS or sham treatment to promote recovery in patients with prolonged DoC

2 weeks

2 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Outcome measures collected one week after treatment

Exploratory Biomarker Assessment

Pre-post intervention-related changes in brain activity using electrophysiology are assessed

1 week

What Are the Treatments Tested in This Trial?

Interventions

• The Brainsonix BX Pulsar 1002

Trial Overview The study tests if Brainsonix BX Pulsar 1002's low-intensity focused ultrasound pulsations (LIFUP) can help recovery in patients with prolonged Disorders of Consciousness (DoC), comparing it against a sham treatment.

How Is the Trial Designed?

Group I: tFUS-tFUS group Active Control 1 Intervention

tFUS-tFUS group will receive 2 sessions of tFUS

Group II: Sham-tFUS group Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Spaulding Rehabilitation Hospital

Collaborator

Trials

143

Recruited

11,200+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Casa Colina Hospital and Centers for Healthcare

Collaborator

Trials

11

Recruited

350+

Published Research Related to This Trial

Multimodal sensory stimulation has strong evidence supporting its effectiveness in improving arousal and clinical outcomes for individuals in a coma or persistent vegetative state following traumatic brain injury, based on a systematic review of studies published between 2008 and 2013.

Auditory stimulation showed moderate evidence of effectiveness, while more complex stimuli had limited evidence, indicating that tailored interventions should be frequent and sustained to maximize recovery potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Sensory Stimulation to Improve Arousal and Alertness of People in a Coma or Persistent Vegetative State After Traumatic Brain Injury: A Systematic Review. Padilla, R., Domina, A.[2022]

Transcranial ultrasound stimulation (TUS) can non-invasively target both cortical and deep brain structures with high spatial resolution, potentially allowing for precise neuromodulation that was previously only possible with invasive methods.

The mechanism of TUS involves ultrasound waves interacting with neuronal membranes, leading to changes in neuronal excitability, which could have significant implications for both basic research and clinical applications in neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial ultrasound stimulation for neuromodulation. Darmani, G., Bergmann, TO., Butts Pauly, K., et al.[2022]

In a study involving 12 healthy participants, transcranial pulse stimulation (TPS) was shown to significantly enhance the efficiency of the cortical sensorimotor network and improve axonal status in the stimulated area, indicating positive neuroplastic changes.

The effects of TPS were observed to last up to one week after stimulation, suggesting its potential for long-term benefits in treating neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. Matt, E., Kaindl, L., Tenk, S., et al.[2022]

The new transcranial pulse stimulation (TPS) technique using ultrashort ultrasound pulses shows promising safety and efficacy in modulating brain activity, with preclinical studies indicating large safety margins and effective neuromodulation.

In a clinical pilot study involving 35 Alzheimer's patients, TPS treatment led to significant improvements in neuropsychological scores, with effects lasting up to three months and correlating with enhanced memory network activity as shown by fMRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Beisteiner, R., Matt, E., Fan, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06939348

NCT06939348 | Ultrasound Stimulation for Patients in a ... 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.

2. withpower.com withpower.com/trial/ultrasound-stimulation-for-disorders-of-consciousness-1319b

Ultrasound Stimulation for Disorders of Consciousness Research suggests that non-invasive brain stimulation, like the Brainsonix BX Pulsar 1002, can be effective for disorders of consciousness. Studies show that ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11219564/

Current state of clinical ultrasound neuromodulation - PMC No outcomes analyzed. Stern et al. (2021), 8 DRE patients, Open-label, uncontrolled, Focused navigated system (BX Pulsar, Brainsonix), Anterior ...

4. allclinicaltrials.com allclinicaltrials.com/study/NCT06939348

Ultrasound Stimulation for Patients in a Disorder of ... 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.

5. mdpi.com mdpi.com/2306-5354/11/11/1126

Preliminary Examination of the Effects of Focused ... As such, this study aimed to explore the safety of the BrainSonix BX Pulsar 1002 Focused Ultrasonic Pulsation Device at a stimulation of ISPTA.3 ≤ 14 W/cm2 by ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06939348

Ultrasound Stimulation for Patients in a Disorder of ... Device : The Brainsonix BX Pulsar 1002 was designed to deliver low-intensity focused ultrasound pulsations (LIFUP) to the human brain. Other Study ID Numbers.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34198105/

Safety of focused ultrasound neuromodulation in humans ... Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X21001224

Safety of focused ultrasound neuromodulation in humans ... Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed ...

9. teams.semel.ucla.edu teams.semel.ucla.edu/sites/default/files/users/user-739/bxpulsar1002_user_manual_053019.pdf

BrainSonix Corp. Currently, use of the BX. Pulsar 1002 is limited by an Investigational Device Exemption (IDE) from the FDA. Users must be trained in operation of the device.