Low-Intensity Focused Ultrasound for Brain Modulation

Overseen By Danielle E Clark, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Benzodiazepines, Anticonvulsants, Psychotropics

Disqualifiers: Suicidal ideation, Substance use, DSM-5 disorders, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach called low-intensity focused ultrasound (LIFU) to examine its effects on certain brain pathways. The researchers aim to understand how different doses of LIFU can alter brain activity, particularly in areas associated with mental health conditions. Participants will receive either a single dose or multiple doses of this ultrasound treatment to observe its influence on brain function. Individuals with stable mental health, without major psychiatric disorders, and who can complete MRI scans might be suitable for this trial. As an unphased study, this trial provides a unique opportunity to contribute to groundbreaking research in mental health treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking benzodiazepines or anticonvulsants at least 7 days before participating, and you cannot use any psychotropic medications during the trial.

What prior data suggests that this low-intensity focused ultrasound is safe for brain modulation?

Research has shown that low-intensity focused ultrasound (LIFU) is generally safe and well-tolerated in people. One study found that a single session of LIFU, up to 8 watts per square centimeter, was safe for stroke patients. This finding suggests that LIFU can also be safely used for other conditions. Another report highlighted LIFU's safety for neuromodulation, which involves using sound waves to alter brain activity. These studies indicate that LIFU does not cause significant side effects, making it a promising option for brain treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about low-intensity focused ultrasound for brain modulation because it offers a non-invasive way to influence brain activity, unlike traditional treatments like medication or surgery. This method uses sound waves to target specific brain areas without needing incisions or drugs, potentially reducing side effects. It's unique because it allows precise targeting and modulation of brain regions, which could open up new possibilities for conditions like depression or neurological disorders. Additionally, the use of ultrasound means adjustments can be made based on real-time feedback, providing a more personalized approach to treatment.

What evidence suggests that low-intensity focused ultrasound is effective for brain modulation?

Research has shown that low-intensity focused ultrasound (LIFU) can alter brain activity without surgery. In this trial, participants will receive either a single dose (1-epoch) or multiple doses (3-epoch) of LIFU. Earlier studies demonstrated that LIFU accurately reached deep brain regions, particularly the front part of a key area. This suggests potential benefits for brain circuits involved in mental health issues. Early results from other trials appeared promising for treating essential tremor, a movement disorder. This technology uses sound waves to target brain tissue, offering a potential new method to manage complex brain conditions. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy individuals who can participate in a study to understand how low-intensity focused ultrasound (LIFU) affects deep brain structures. Specific eligibility criteria are not provided, but typically participants must be in good health and meet certain age and consent requirements.

Inclusion Criteria

Body mass index 17-38 kg/m2

Fluent English speaker, capable of providing written informed consent

Overall Anxiety Severity and Impairment Scale <8 and Patient Health Questionnaire-9 <10

Exclusion Criteria

No telephone or easy access to telephone

Has active suicidal ideation (as measured by Suicide-Risk-Assessment-C-SSRS 'Yes' answers to items 3, 4, or 5 Suicidal Ideation-Past 1 month section, or any 'Yes' answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months

Has positive test result(s) for alcohol of abuse (including methadone, opiates, cocaine, amphetamine/methamphetamine and ecstasy), or substance use disorder including alcohol, stimulants, sedatives, and cannabis exceeding mild severity in the last 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity focused ultrasound (LIFU) applied to deep white matter tracts, with one or three epochs of sonication

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in functional connectivity using fMRI post-sonication

Up to 30 minutes post-sonication

Data Analysis

Analysis of fMRI data to determine dose-response relationships and functional connectivity changes

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound

Trial Overview The study is testing the effects of different doses of LIFU on the human brain's white matter tracts. It builds on previous findings that suggest LIFU can target specific brain areas noninvasively. The goal is to pave the way for future clinical trials in psychiatric disorders.

How Is the Trial Designed?

Group I: Single Dose (1-epoch) Experimental Treatment 1 Intervention

An 80-second train of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts). It is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 estimated derated ISPPA). Any modeling of actual energy delivery will be made a posteriori employing BabelBrain® software embedded in the Brainsight® neuronavigation system.

Group II: Multiple Doses (3-epoch) Experimental Treatment 1 Intervention

Three 80-second trains of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts) will be administered, separated by 30 seconds each. Again, it is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 derated ISPPA). See above for a posteriori acoustic energy modeling.

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11700779/

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

A Comprehensive Review of Low-Intensity Focused ... In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound technology, comparing it ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05997030

Low-Intensity Focused Ultrasound (LIFU) Neuromodulation It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

4. fusfoundation.org fusfoundation.org/posts/essential-tremor-neuromodulation-clinical-trial-begins-in-california/

Essential Tremor Neuromodulation Clinical Trial Begins in ... Up to 60 participants will be enrolled in a clinical trial studying low-intensity focused ultrasound (LIFU) neuromodulation for treating ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.872639/full

Current State of Potential Mechanisms Supporting Low ... This review provides a comprehensive introduction to the underlying mechanics of both acoustic energy and neuronal membranes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599299/

Safety of Clinical Ultrasound Neuromodulation - PMC Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000178

Low intensity focused ultrasound stimulation in stroke Our phase-I safety study suggests that one session of LIFUS up to 8 W/cm2 ISPPA is safe and feasible in stroke patients, and LIFUS at high intensity induces ...

8. nature.com nature.com/articles/s41598-020-62265-8

A retrospective qualitative report of symptoms and safety ... We provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of ...