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

Trial Summary

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 data supports the effectiveness of the treatment The Brainsonix BX Pulsar 1002 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 sensory and auditory stimulation can improve alertness and arousal in patients with these conditions. ^{1 2 3 4 5}

Is ultrasound stimulation safe for use in humans?

Research on ultrasound brain stimulation, including studies on Alzheimer's patients and healthy volunteers, shows it is generally safe with high treatment tolerability and no major side effects reported. Clinical evaluations and imaging studies have not revealed any adverse effects, suggesting it is a safe method for neuromodulation. ^{6 7 8 9 10}

How does the Brainsonix BX Pulsar 1002 treatment differ from other treatments for disorders of consciousness?

The Brainsonix BX Pulsar 1002 treatment is unique because it uses ultrasound to non-invasively target deep brain structures with high precision, which is not possible with other non-invasive treatments. This method can modulate brain activity in a focused way, potentially aiding recovery in patients with disorders of consciousness by stimulating specific brain areas like the thalamus. ^{6 8 10 11 12}

What is the purpose of this trial?

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.

Research Team

Martin M Monti, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Music as a diagnostic tool in low awareness states: considering limbic responses. [2019]

3. United States 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. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Effect of acoustic stimuli in patients with disorders of consciousness: a quantitative electroencephalography study. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Information processing in patients in vegetative and minimally conscious states. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Development of a wireless ultrasonic brain stimulation system for concurrent bilateral neuromodulation in freely moving rodents. [2022]

9. England pubmed.ncbi.nlm.nih.gov

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial ultrasound stimulation for neuromodulation. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Ultrasonic Deep Brain Neuromodulation in Acute Disorders of Consciousness: A Proof-of-Concept. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Ultrasonically-assisted intracortical microstimulation of the rat. [2020]