Focused Ultrasound for Seizures

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to reduce seizures in individuals with ongoing non-convulsive or focal motor seizures unresponsive to standard treatments. The researchers use Pulsed Low-Intensity Focused Ultrasound (PLIFU) to target specific brain regions and calm seizure activity. Participants will undergo up to two sessions of this focused ultrasound therapy. Candidates for this trial include those who continue to experience seizures despite using at least two anti-seizure medications and are monitored in an ICU with EEG (a brain activity test). As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for challenging seizure conditions.

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 prior data suggests that Pulsed Low-Intensity Focused Ultrasound is safe for treating seizures?

Research has shown that Pulsed Low-Intensity Focused Ultrasound (PLIFU) is a safe and non-invasive treatment. Studies indicate that this type of ultrasound can target specific areas of the brain without harming nearby tissue.

In earlier trials, PLIFU reduced or stopped epileptic activity, suggesting it can help with seizures without serious side effects. However, while early results are promising, more research is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about PLIFU, or Pulsed Low-Intensity Focused Ultrasound, because it offers a non-invasive approach to treating seizures, specifically in cases of non-convulsive or focal motor status epilepticus (SE) that resist current anti-seizure medications (ASMs). Unlike standard treatments that often rely on medication to control electrical activity in the brain, PLIFU uses focused ultrasound waves to target and potentially modulate brain activity directly. This method could minimize side effects associated with drugs and provide faster relief for those not responding to traditional treatments. By harnessing this cutting-edge technology, PLIFU might offer a new hope for patients struggling with hard-to-treat seizures.

What evidence suggests that PLIFU is effective for reducing seizures in NCSE/FMSE?

Research shows that Pulsed Low-Intensity Focused Ultrasound (PLIFU), the treatment under study in this trial, may help reduce seizures. Animal studies found that this method can lower seizure activity without harming brain tissue. In early human trials, PLIFU changed brain activity related to seizures, offering hope for people with medication-resistant epilepsy. Additionally, PLIFU affected seizure activity for extended periods, sometimes up to seven weeks. These findings suggest that PLIFU could be a useful treatment for certain types of epilepsy that don't improve with standard drugs. ^{2 5 6 7 8}

Who Is on the Research Team?

Imran Quraishi, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05784805

Acute Effects of Focused Ultrasound Modulation on EEG ... The primary objective of this study is to determine whether PLIFU reduces or suppresses epileptic activity in patients with Non-Convulsive Status Epilepticus ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9684587/

Low Intensity Focused Ultrasound for Epilepsy Several preclinical studies have demonstrated the ability of LIFUS to suppress seizures in epilepsy animal models without damaging tissue. Resection after ...

3. karger.com karger.com/doi/10.1159/000545716

Focused Ultrasound in the Treatment of Epilepsy A Safety, Tolerability, and Preliminary Efficacy of Low-Intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Epilepsy ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/brb3.2852

Low‐intensity focused ultrasound, a novel approach to ... The objective of this short review was to evaluate current treatment options and low-intensity, pulsed-focused ultrasound (FUS) as a potential new treatment ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923010899

Pulsed-Focused Ultrasound Provides Long-Term ... This study demonstrates that low-intensity pulsed ultrasound can modulate epileptiform activity for up to 7 weeks.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9847596/

Low‐intensity focused ultrasound, a novel approach to ... The objective of this short review was to evaluate current treatment options and low‐intensity, pulsed‐focused ultrasound (FUS) as a potential new treatment ...

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

Safety of focused ultrasound neuromodulation in humans ... Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed ...