Focused Ultrasound for Seizures

Recruiting in New Haven (>99 mi)

Overseen By Imran Quraishi, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: ASMs

Disqualifiers: Pregnancy, Implanted device, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, the investigators propose Pulsed Low-Intensity Focused Ultrasound (PLIFU) stimulation of brain regions that modulate (thalamus) or generate focal motor seizures (primary motor cortex), with the goal of ameliorating seizure activity in subjects in non-convulsive or focal motor status epilepticus. The course of treatment will consist of an initial 10 minute PLIFU treatment session with an option for a 2nd session if necessary. The primary objective of this study is to determine whether PLIFU reduces or suppresses epileptic activity in patients with Non-Convulsive Status Epilepticus (NCSE)/Focal Motor Status Epilepticus (FMSE) that have not responded to standard of care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that participants have ongoing seizures despite treatment with at least two anti-seizure medications.

What data supports the effectiveness of the treatment PLIFU for seizures?

Research shows that pulsed low-intensity focused ultrasound (PLIFU) can reduce seizure activity in animal models of epilepsy by decreasing abnormal brain activity and improving brain network connections. Additionally, PLIFU has been safely used in humans with epilepsy, showing promise as a non-invasive treatment option. ^{1 2 3 4 5}

Is focused ultrasound safe for treating seizures?

Focused ultrasound, including forms like PLIFU and LIFU, has been shown to be generally safe in humans and animals, with studies reporting no adverse events in human trials for epilepsy. It is a non-invasive technique that targets specific brain areas without causing damage, and any side effects are typically mild and temporary. ^{1 2 4 6 7}

How is the treatment PLIFU different from other treatments for seizures?

PLIFU (Pulsed Low-Intensity Focused Ultrasound) is unique because it is a noninvasive treatment that uses focused sound waves to target specific brain areas, like the hippocampus, without surgery or radiation. It offers a novel way to modulate brain activity and potentially suppress seizures in patients with drug-resistant epilepsy, providing an alternative for those who cannot undergo surgery. ^{1 2 3 4 5}

Research Team

Imran Quraishi, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for patients with ongoing non-convulsive or focal motor status epilepticus who haven't improved after two anti-seizure medications. They must be in the ICU, monitored by EEG, and have consent from a legal representative. It's not for those with cranial implants, pregnancy, metal in the head, recent other trials participation, or TENS unit use.

Inclusion Criteria

You have been diagnosed with persistent non-convulsive or focal motor seizures despite receiving treatment from two antiepileptic medications.

You have provided a signed and dated consent form authorized by your legal representative.

You were admitted to the ICU and monitored with scalp EEG electrodes in a continuous manner.

Exclusion Criteria

Unable to obtain informed consent

You have a device implanted in your brain to treat epilepsy.

You are pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Pulsed Low-Intensity Focused Ultrasound (PLIFU) treatment for 10 minutes, with an option for a second session if necessary

1 day

1-2 visits (in-person)

Follow-up

Participants are monitored for changes in epileptic activity using continuous surface EEG

1-2 days

Treatment Details

Interventions

• PLIFU

Trial Overview The study tests Pulsed Low-Intensity Focused Ultrasound (PLIFU) on brain areas linked to seizures. The goal is to see if PLIFU can reduce seizure activity when standard treatments fail. Participants will undergo an initial 10-minute session of PLIFU with a possible second round if needed.

Participant Groups

Group I: Participants with ongoing non-convulsive or focal motor SE Experimental Treatment 1 Intervention

Adult patients with ongoing non-convulsive or focal motor SE despite treatment with at least 2 ASMs and who are monitored with surface EEG will be screened and enrolled to receive up to 2 sessions of PLIFU.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Swebilius Foundation

Collaborator

Trials

1

Recruited

10+

Findings from Research

Low-intensity, pulsed focused ultrasound (FUS) significantly reduced the occurrence of epileptic EEG bursts in a rat model of epilepsy, indicating its potential efficacy in suppressing seizure activity.

The FUS treatment was non-invasive and did not cause any damage to brain tissue, suggesting it could be a safe alternative for treating epilepsy without the risks associated with invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. Min, BK., Bystritsky, A., Jung, KI., et al.[2022]

Low intensity focused ultrasound (LIFUS) is a promising noninvasive treatment for drug-resistant epilepsy (DRE), showing potential to suppress seizures without damaging brain tissue, as demonstrated in preclinical studies and initial trials in humans.

LIFUS can precisely target specific brain regions, making it a novel alternative to traditional electrostimulatory devices, which are often palliative and not suitable for all patients, thus expanding treatment options for those with DRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Epilepsy- A New Approach to Neuromodulation. Bubrick, EJ., McDannold, NJ., White, PJ.[2022]

Low-intensity focused ultrasound (LIFU) effectively altered the functional brain network in epileptic rats, leading to a significant reduction in network connection strength across multiple brain regions after treatment.

The study demonstrated that LIFU can modify key brain network indicators, suggesting its potential as a noninvasive treatment for epilepsy by disrupting abnormal neuronal synchronization associated with seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity. Zhang, M., Li, B., Lv, X., et al.[2021]

The study successfully developed a laboratory device to deliver pulsed low-intensity focused ultrasound (PLIFUS) to the hippocampus in a patient with drug-resistant temporal lobe epilepsy, marking a first-in-human application.

The treatment was administered safely with no adverse events reported, suggesting that PLIFUS could be a promising therapeutic option for neuromodulation in neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Platform for Investigating Therapeutic Neuromodulation Across the Human Hippocampus. Brinker, ST., Preiswerk, F., White, PJ., et al.[2021]

In a study involving 44 male Sprague-Dawley rats, focused ultrasound (FUS) significantly reduced EEG epileptiform spikes by about 25% and bursts by about 33%, demonstrating its potential to modulate brain activity in a model of temporal lobe epilepsy.

The most effective FUS regimen used a higher intensity (0.75-MI, ISPTA 2.8 W/cm2) and longer duration (10 minutes), which not only suppressed epileptiform activity but also provided protective effects on hippocampal tissue lasting up to 14 weeks, suggesting a promising avenue for epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed-Focused Ultrasound Provides Long-Term Suppression of Epileptiform Bursts in the Kainic Acid-Induced Epilepsy Rat Model. Chu, PC., Yu, HY., Lee, CC., et al.[2022]

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]

Transcranial focused ultrasound (tFUS) can precisely target specific brain areas with low acoustic intensity, effectively modulating brain excitability and potentially promoting neural plasticity for neurorehabilitation.

The review highlights the excellent safety profile of tFUS, but emphasizes the need for new safety guidelines and recommendations for its use in healthy volunteers and clinical settings, based on a comprehensive analysis of acoustic parameters and their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. Lee, W., Weisholtz, DS., Strangman, GE., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. [2022]

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

Low Intensity Focused Ultrasound for Epilepsy- A New Approach to Neuromodulation. [2022]

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

Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Platform for Investigating Therapeutic Neuromodulation Across the Human Hippocampus. [2021]

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

Pulsed-Focused Ultrasound Provides Long-Term Suppression of Epileptiform Bursts in the Kainic Acid-Induced Epilepsy Rat Model. [2022]

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

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

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. [2023]