Focused Ultrasound for Epilepsy

(LIFUS Trial)

Overseen By Lillian H Stapelfeld, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with drug-resistant temporal lobe epilepsy using Pulsed Low-Intensity Focused Ultrasound (PLIFUS). The goal is to determine if this treatment remains effective and tolerable over time. It suits those who have tried at least two epilepsy medications without success and experience seizures affecting awareness at least once or twice a month. Participants must be able to track their seizures or have someone who can do it for them. As an unphased trial, this study provides a unique opportunity to contribute to pioneering research that could lead to new treatment options for epilepsy.

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 prior data suggests that this technique is safe for patients with drug-resistant temporal lobe epilepsy?

Research has shown that pulsed low-intensity focused ultrasound (PLIFUS) might be a safe way to treat epilepsy. Studies have found that this technique can reduce seizures in animals without damaging brain tissue, suggesting potential safety for humans as well.

One study examined the use of PLIFUS to target specific brain areas where seizures originate. The aim was to lessen seizures, and the results were promising. Although specific information on side effects in humans is not yet available, the ongoing testing of this treatment indicates that early results are encouraging enough to proceed with human trials.

Overall, PLIFUS appears to be a promising and potentially safe option for individuals with epilepsy that does not respond to medication. However, like any treatment, it is important to understand the possible risks and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about PLIFUS, or Pulsed Low Intensity Focused Ultrasound, for drug-resistant epilepsy because it offers a non-invasive approach, unlike traditional treatments such as anti-seizure medications or surgical interventions. Most current treatments aim to control seizures through medication or remove the affected brain tissue surgically. However, PLIFUS uses sound waves to target and potentially disrupt the abnormal brain activity causing seizures, without the need for incisions or drugs. This method could lead to fewer side effects and a quicker recovery time, making it a promising alternative for those who haven't responded well to existing therapies.

What evidence suggests that PLIFUS might be an effective treatment for epilepsy?

Research has shown that Pulsed Low-Intensity Focused Ultrasound (PLIFUS), the treatment under study in this trial, might help reduce seizures in people with drug-resistant temporal lobe epilepsy. Animal studies have found that this type of ultrasound can lower seizure activity without damaging brain tissue. In some human studies, PLIFUS reduced the number of seizures by 50%–60% over time. This suggests the treatment could benefit those who don't respond well to medication. The procedure involves directing ultrasound waves at the brain areas involved in seizures, potentially calming the overactive brain cells causing them. ^{1 2 5 6 7}

Who Is on the Research Team?

Ellen J Bubrick, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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]

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]

Citations

1. 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 ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/93/NCT03868293/Prot_SAP_000.pdf

Low Intensity Focused Ultrasound Treatment for Drug- ... In this study, we propose long-term, repeated PLIFUS stimulation of brain regions containing epileptic tissue, with the goal of decreasing seizure activity in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9297900/

Pilot study of focused ultrasound for drug‐resistant epilepsy They were proved to be effective in reducing seizure frequency by 50%–60% in long‐term treatment. Current neuromodulation devices also ...

4. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.886584/full

Recent Advances in the Use of Focused Ultrasound as a ... Approximately one third of patients with epilepsy are drug-resistant (DRE). Resective surgery is an effective treatment for DRE, yet invasive, and not all DRE ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05947656

Evaluation of the NaviFUS System in Drug Resistant Epilepsy In this clinical study, the NaviFUS System is intended to deliver low intensity FUS to generate neuromodulation effects on a predetermined treatment region (one ...

6. aesnet.org aesnet.org/about/aes-press-room/press-releases/low-intensity-focused-ultrasound-treatment-holds-promise-as--non-invasive-treatment-for-common-epilepsy--suggests-early-research

Low-Intensity Focused Ultrasound Treatment Holds Promise ... A non-invasive technique called low-intensity focused ultrasound (LOFU) holds promise for treating and preventing seizures in the most common form of epilepsy.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0035378723011451

Focused ultrasounds: What is their future in epileptology? ... High intensity focused ultrasounds (HIFU) are being increasingly advocated as a useful tool in the management of focal drug-resistant epilepsy.