Transcranial Focused Ultrasound Safety in Healthy Subjects

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical University of South Carolina

Must not be taking: Psychotropics, Stimulants, Steroids, others

Disqualifiers: Psychiatric diagnosis, CNS disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new wearable device called Attune ATTN201 that uses sound waves to stimulate specific parts of the brain. It focuses on people whose brain activity is being studied. The device aims to change brain activity by sending sound waves to precise areas without affecting other parts of the brain.

Will I have to stop taking my current medications?

The trial requires that you stop taking any psychotropic medications (drugs that affect your mood, thoughts, or behavior) at least 5 half-lives (the time it takes for the drug's active substance to reduce by half in your body) before the procedure. Additionally, you cannot be taking medications like stimulants, modafinil, thyroid medication, or steroids.

What data supports the effectiveness of the treatment Transcranial Focused Ultrasound?

Research shows that MR-guided focused ultrasound (MRgFUS), a type of transcranial focused ultrasound, is effective in treating conditions like Parkinson's disease, essential tremor, and neuropathic pain. It is a non-invasive method that can precisely target and treat areas in the brain, offering an alternative to traditional surgery with fewer complications. ^{1 2 3 4 5}

Is transcranial focused ultrasound generally safe for humans?

Research shows that transcranial focused ultrasound, including MR-guided focused ultrasound (MRgFUS), is generally safe for humans. Studies have demonstrated its safety in treating brain tumors, Parkinson's disease, essential tremor, and neuropathic pain, with low complication rates and no significant adverse effects when used correctly. ^{2 6 7 8 9}

How is transcranial focused ultrasound treatment different from other treatments?

Transcranial focused ultrasound (tFUS) is unique because it is a non-invasive treatment that uses sound waves to target and treat specific areas in the brain without the need for surgery or anesthesia. It is guided by MRI, which allows for precise targeting and monitoring, and it does not involve ionizing radiation, reducing the risk of complications. ^{2 7 8 10 11}

Research Team

Eligibility Criteria

This trial is for healthy adults aged 22-55 who speak English, can consent, and have no history of mental or physical illness. Women must not be pregnant and participants should not have metal implants. All must commit to the study schedule.

Inclusion Criteria

English as a primary language

I am able to understand and agree to the study's requirements.

Willingness to adhere to the tFUS study schedule and assessments

Exclusion Criteria

Implanted devices/ferrous metal of any kind

I cannot complete tests that measure my thinking skills.

I have no history of major brain disorders or injuries.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound stimulation using the Attune ATTN201 device over the course of 1 month

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including EEG recordings and behavioral assessments

2 years

Treatment Details

Interventions

• Transcranial Focused Ultrasound (Focused Ultrasound)

Trial Overview The study tests a device called Attune ATTN201 using Transcranial Focused Ultrasound (tFUS) on the Central Medial Thalamus in the brain to see how it affects sleep induction and brain activity without harming surrounding tissue.

Participant Groups

Group I: Focused Ultrasound Dose #8 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using high frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group II: Focused Ultrasound Dose #7 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using medium frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group III: Focused Ultrasound Dose #6 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using low frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group IV: Focused Ultrasound Dose #3 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using low frequency stimulation as condition 4. Stimulation will last 1-10 minutes.

Group V: Focused Ultrasound Dose #2 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using medium frequency stimulation as condition 2. Stimulation will last 1-10 minutes.

Group VI: Focused Ultrasound Dose #1 Experimental Treatment 1 Intervention

Focused Ultrasound will be administered using high frequency stimulation as condition 1. Stimulation will last 1-10 minutes.

Group VII: Focused Ultrasound Dose #5 Placebo Group 1 Intervention

Focused Ultrasound will be administered using the sham condition.

Group VIII: Focused Ultrasound Dose #4 Placebo Group 1 Intervention

Focused Ultrasound will be administered using the sham condition.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Dr. Erik Summers

Medical University of South Carolina

Chief Medical Officer

MD from University of Alabama at Birmingham

Dr. Patrick J. Cawley

Medical University of South Carolina

Chief Executive Officer

MD, MBA

Attune Neurosciences

Collaborator

Trials

1

Recruited

30+

Attune Neurosciences Inc

Industry Sponsor

Trials

1

Recruited

30+

Findings from Research

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

MR-guided focused ultrasound (MRgFUS) is a promising non-invasive technique for treating deep brain conditions, showing effectiveness in chronic diseases like Parkinson's and essential tremor, as well as in neuropathic pain.

The method is advantageous because it does not require anesthesia, avoids ionizing radiation, and has low complication rates, making it a safer alternative to traditional neurosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound: a new generation treatment of Parkinson's disease, essential tremor and neuropathic pain. Dobrakowski, PP., Machowska-Majchrzak, AK., Labuz-Roszak, B., et al.[2021]

Transcranial MR-guided Focused Ultrasound Surgery (MRgFUS) has shown promising results in treating conditions like neuropathic pain and essential tremor, with most patients experiencing significant symptom improvement after treatment.

Despite its potential, there are safety concerns, as serious adverse effects, including intracranial hemorrhages, were reported in two cases due to cavitation during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial brain ablation with high-intensity focused ultrasound. Jenne, JW.[2014]

The study demonstrated that enhanced magnetic resonance-guided focused ultrasound (MRgFUS) can create ablations that are, on average, 1.8 times larger than those produced by standard sonication using the same energy, indicating improved efficacy.

The enhanced MRgFUS method was found to be safe and controllable, with predictable ablation locations and consistent thermal damage patterns, suggesting it could significantly shorten tumor ablation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery using an enhanced sonication technique in a pig muscle model. Kopelman, D., Inbar, Y., Hanannel, A., et al.[2019]

Transcranial MR-guided focused ultrasound (MRgFUS) is an innovative, non-invasive technique that can effectively treat movement disorders like essential tremor through thermoablation, eliminating the need for open surgery.

The technology is also being explored for its ability to open the blood-brain barrier using microbubbles, which could enhance targeted drug delivery to the brain, potentially improving treatment options for various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Principles and Clinical Workflow of Transcranial MR-Guided Focused Ultrasound. Meng, Y., Jones, RM., Davidson, B., et al.[2021]

Microfocused Ultrasound with Visualization (MFU-V) has a well-established safety profile, showing only mild and transient side effects like tenderness and redness, with rare adverse events typically linked to improper technique.

When used correctly, MFU-V treatments are safe, with most side effects resolving quickly and without lasting effects, indicating its efficacy in cosmetic dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. Hitchcock, TM., Dobke, MK.[2022]

A 63-year-old patient with a recurrent glioblastoma underwent transcranial MR-guided focused ultrasound surgery (MRgFUS), demonstrating the feasibility of this noninvasive technique for brain tumor ablation.

The procedure involved 25 high-power sonications and successfully achieved partial tumor ablation without causing neurological deficits or adverse effects, highlighting its safety and potential for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. Coluccia, D., Fandino, J., Schwyzer, L., et al.[2020]

In a study involving 30 women with breast cancer, MRgFUS treatment resulted in an impressive average of 96.9% tumor necrosis, indicating its high effectiveness in ablating breast carcinomas.

The procedure was well tolerated with minimal adverse effects, especially when performed under local anesthesia, suggesting it could be a safe noninvasive alternative to traditional surgical methods like lumpectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. Furusawa, H., Namba, K., Thomsen, S., et al.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) therapy for uterine fibroids has a relatively low incidence of serious complications, with major adverse events occurring in only 0.41% of cases across 43 studies analyzed.

The most common adverse events reported include pain, skin burns, urinary tract infections, and sciatic neuropraxia, with an overall adverse event occurrence rate of 24.67%, indicating that while MRgFUS is generally safe, some side effects do occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

The dual-channel radiofrequency receive-only head coil significantly improves imaging quality in tcMRgFUS, providing up to 4 times better signal-to-noise ratio (SNR) compared to the standard body coil, which enhances visualization of critical brain structures.

The head coil also improves MR thermometry accuracy, reducing temperature uncertainty from 0.96°C to 0.41°C, allowing for more precise monitoring of thermal ablation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. Bitton, RR., Sheingaouz, E., Assif, B., et al.[2021]

The study presents a validated, open-source MR-guided focused ultrasound (MRgFUS) system that allows for precise and controllable thermal and mechanical treatments in small animals, which could enhance research in various medical applications.

This system has been successfully tested in tissue-mimicking phantoms and live mice, demonstrating accurate temperature control and effective treatment delivery, making it a cost-effective option for researchers interested in MRgFUS technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-source, small-animal magnetic resonance-guided focused ultrasound system. Poorman, ME., Chaplin, VL., Wilkens, K., et al.[2023]

References

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

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

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

MR-guided focused ultrasound: a new generation treatment of Parkinson's disease, essential tremor and neuropathic pain. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial brain ablation with high-intensity focused ultrasound. [2014]

4. Ireland pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery using an enhanced sonication technique in a pig muscle model. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Technical Principles and Clinical Workflow of Transcranial MR-Guided Focused Ultrasound. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Review of the safety profile for microfocused ultrasound with visualization. [2022]

7. England pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. [2020]

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

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. [2022]

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

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Open-source, small-animal magnetic resonance-guided focused ultrasound system. [2023]