Focused Ultrasound for Epilepsy

(LIFUS Trial)

Overseen By Janet S Orozco, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Dementia, Psychosis, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 9

Duration: 3 weeks

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that if you have a Vagal Nerve Stimulator, it will be turned off during treatment sessions and turned back on afterward.

What data supports the effectiveness of the treatment PLIFUS for epilepsy?

Research shows that low-intensity focused ultrasound (LIFUS) can safely and noninvasively target brain areas to help control seizures in epilepsy, as seen in animal studies and initial human trials. This treatment has been shown to modulate brain activity without causing damage, offering a promising alternative for patients with drug-resistant epilepsy. ^{1 2 3 4 5}

How is the treatment PLIFUS different from other epilepsy treatments?

PLIFUS is a unique, non-invasive treatment that uses focused ultrasound to target specific brain areas without surgery or radiation, offering a new option for patients with drug-resistant epilepsy who cannot undergo surgery. It works by modulating brain activity through precise acoustic energy, potentially reducing seizures without damaging brain tissue. ^{2 3 4 5 6}

What is the purpose of this trial?

The aim of the proposed pilot study is to investigate patient tolerability and efficacy of moderate term, repeated exposure of Pulsed Low-Intensity Focused Ultrasound (PLIFUS) in patients with drug-resistant temporal lobe epilepsy.

Research Team

Ellen J Bubrick, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults with drug-resistant temporal lobe epilepsy, experiencing 1-2 seizures monthly. Participants must be able to log seizure frequency and understand the consent form. They should have failed at least two antiepileptic drug trials.

Inclusion Criteria

You can read and understand the consent form, and talk about any symptoms you might have during or after treatments.

I have temporal lobe epilepsy that hasn't improved with at least two different seizure medications.

I have 1-2 seizures monthly and can track them myself or with help.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Seizure Logging

Participants keep track of their seizure events in the Daily Seizure Log Diary

4 weeks

No visits required

Treatment

Participants receive Pulsed Low-Intensity Focused Ultrasound (PLIFUS) treatment

3 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• PLIFUS

Trial Overview The study tests the tolerability and effectiveness of Pulsed Low-Intensity Focused Ultrasound (PLIFUS) on patients with drug-resistant temporal lobe epilepsy through moderate term, repeated exposure.

Participant Groups

Group I: Drug-Resistant Epilepsy (temporal lobe) Experimental Treatment 1 Intervention

Pulsed low intensity focused ultrasound

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

MR-guided focused ultrasound (MRgFUS) is emerging as a promising minimally invasive treatment for drug-resistant epilepsy, offering potential benefits such as thermoablation and neuromodulation without the risks associated with traditional surgical methods.

Current studies suggest that high-intensity ultrasound may effectively target lesions in the anterior thalamus, while low-intensity ultrasound could modulate the hippocampus, but further research is needed to ensure these strategies are safe and effective for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now? Labate, A., Bertino, S., Morabito, R., et al.[2023]

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 (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]

Focused ultrasound (FUS) can be safely applied to the seizure onset zone in patients with drug-resistant epilepsy, with no significant adverse effects like brain lesions or edema observed in the six patients studied.

While two patients experienced a decrease in seizure frequency after FUS treatment, one patient had an increase in subclinical seizures, indicating that further research with a larger cohort is needed to better understand the efficacy and optimal parameters for FUS in seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of focused ultrasound for drug-resistant epilepsy. Lee, CC., Chou, CC., Hsiao, FJ., et al.[2022]

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 (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]

References

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

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now? [2023]

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

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

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

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

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

Pilot study of focused ultrasound for drug-resistant epilepsy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

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