Focused Ultrasound for Temporal Lobe Epilepsy

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: BrainSonix Inc.

Must be taking: Antiepileptic drugs

Disqualifiers: Cognitive disorder, Dementia, Psychotic symptoms, Severe cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat temporal lobe epilepsy using focused ultrasound, a technique that can stimulate or calm brain activity without damaging brain tissue. The researchers aim to determine if this approach can be detected using special brain scans and if it is a safe option. It targets individuals who continue to experience seizures despite trying at least three different epilepsy medications and who might require brain surgery. As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research in epilepsy treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves patients with epilepsy who have not responded to at least three antiepileptic drugs, it seems likely that you may continue your current medications.

What prior data suggests that this technique is safe for epilepsy patients?

Research shows that low-intensity focused ultrasound pulsation (LIFUP) could be a promising way to manage epilepsy without surgery or radiation. In animal studies, LIFUP has not harmed brain tissue, suggesting it might be safe for humans as well. However, its safety in people still requires thorough assessment.

Some studies indicate that ultrasound stimulation can reduce seizures and improve behavior in animals with epilepsy. This is encouraging, but more research is needed to confirm these results in humans.

Overall, LIFUP appears to be well-tolerated, but gathering safety information for humans remains crucial. Prospective participants in a clinical trial for LIFUP should ask questions and discuss any concerns with medical professionals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low-intensity Focused Ultrasound Pulsation (LIFUP) for temporal lobe epilepsy because it offers a non-invasive treatment option that might avoid the side effects of traditional epilepsy medications, which often include dizziness and fatigue. Unlike standard antiepileptic drugs that work by modulating neurotransmitter activity, LIFUP uses sound waves to target and modulate brain activity directly. This innovative approach could potentially provide a more precise and safer way to manage seizures, with fewer side effects and a quicker recovery time compared to surgical interventions.

What evidence suggests that Low-intensity Focused Ultrasound Pulsation is effective for temporal lobe epilepsy?

Research has shown that low-intensity focused ultrasound pulsation (LIFUP), which participants in this trial will receive, can help reduce seizures in people with epilepsy. In a study using a model of temporal lobe epilepsy, ultrasound treatment stopped seizures and improved behavior. This could be especially helpful for the 33% of patients who don't respond to epilepsy medications. While animal studies, such as one where most cats became seizure-free, are promising, more research is needed to determine if these results apply to humans. Overall, LIFUP could offer a non-invasive option for managing epilepsy. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with severe epilepsy that hasn't improved after trying at least three antiepileptic drugs. They should be candidates for a specific type of brain surgery and have evidence of dysfunction in one area of the hippocampus. People can't join if they can't consent, cooperate, or have metal in their head, serious heart issues, certain neurological conditions, or are pregnant.

Inclusion Criteria

My seizures haven't improved despite trying three different epilepsy medications.

I have epilepsy not controlled by medication and have been recommended a specific brain surgery.

My tests show I have a problem with one side of my brain causing seizures.

Exclusion Criteria

Subjects with dementia, delirium and psychotic symptoms

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

I am currently pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound to stimulate or suppress brain activity

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-intensity Focused Ultrasound Pulsation (LIFUP)

Trial Overview The study tests Low-intensity Focused Ultrasound Pulsation (LIFUP) to see if it can stimulate or suppress brain activity without causing damage. This non-invasive technique's effects will be monitored using functional MRI in patients who could benefit from surgical intervention.

How Is the Trial Designed?

Group I: LIFUP Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

BrainSonix Inc.

Lead Sponsor

Trials

1

Recruited

10+

Gerald J. & Dorothy R. Friedman Center for Lymphedema Research & Treatment

Collaborator

Trials

1

Recruited

10+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

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, 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]

This case report presents the first use of transcranial magnetic resonance-guided focused ultrasound (MRgFUS) for treating mesial temporal lobe epilepsy (MTLE), showing promising results as the patient remained almost seizure-free for up to 12 months after the procedure.

Despite challenges in achieving high ablation temperatures due to technical limitations, the findings suggest that MRgFUS could be a safe and feasible treatment option for MTLE, warranting further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. Abe, K., Yamaguchi, T., Hori, H., et al.[2020]

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]

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]

Citations

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

Low Intensity Focused Ultrasound for Epilepsy Ultrasound stimulation inhibits recurrent seizures and improves behavioral outcome in an experimental model of mesial temporal lobe epilepsy. Epilepsy Behav.

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

Low Intensity Focused Ultrasound Treatment for Drug- ... Approximately 67% of patients with epilepsy achieve seizure control with antiepileptic drugs, leaving 33% of patients with persisting seizures despite ...

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

Recent Advances in the Use of Focused Ultrasound as a ... Eight out of the nine surviving cats became seizure free after surgery, whereas 9 out of 11 became seizure free after HIFU. Six cats died after resective ...

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

Focused ultrasounds: What is their future in epileptology? ... Yet, open surgery focusing on the resection of the epileptogenic zone (EZ) results in up to 80% seizure-freedom and is thus deemed superior in terms of seizure ...

5. clinicaltrial.be clinicaltrial.be/en/details/177729?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Low-intensity Focused Ultrasound Pulsation (LIFUP) for Tr... We intend to use focused ultrasound to stimulate or suppress brain activity in patients with epilepsy. We hypothesize that focused ...

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

Safety of focused ultrasound neuromodulation in humans ... Ultrasound stimulation inhibits recurrent seizures and improves behavioral outcome in an experimental model of mesial temporal lobe epilepsy. Epilepsy Behav ...

7. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(15)00738-X/fulltext

Safety and Feasibility of Focused Ultrasound ... Low-intensity focused ultrasound pulsation (LIFUP) offers the potential for non-invasive neuromodulation, and in animal studies has not shown any evidence of ...

8. medrxiv.org medrxiv.org/content/10.1101/2020.04.10.20060855v1

Safety of Focused Ultrasound Neuromodulation in Humans ... However, the safety of LIFUP neuromodulation has not yet been adequately assessed. Patients with refractory temporal lobe epilepsy electing to ...