Non-Invasive Low Intensity Focused Ultrasound Stimulation for Drug-Resistant Epilepsy

NCT07680842 | Recruiting DMC FDA Device

• 1 other identifier: 24-41317
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to investigate the effects of a non-invasive, low intensity focused ultrasound (LIFU) stimulation on seizure frequency and the epileptogenic network in drug-resistant epilepsy. LIFU uses focused sound waves to modulate deep brain regions and to enable changes in brain network activity. Encephalography (EEG) and behavioral tasks will also be used to study how LIFU affects brain activity.

Conditions

Drug-Resistant Epilepsy; Epilepsy; Epilepsy (Treatment Refractory); Epilepsy Comorbidities; Epilepsy, Drug Resistant; Epilepsy, Generalized; Epilepsy, Focal

Keywords

Seizures; Drug-Resistant Epilepsy; Epilepsy; Transcranial Ultrasound Stimulation; Focused ultrasound Stimulation; Electroencephalography (EEG); Low Intensity Focused ultrasound (LIFU)

Outcome Measures

Primary Outcomes (1)

• Seizure Frequency

  Seizure counts will be obtained from a seizure diary kept by each participant.

  Seizure counts will be obtained daily for at least 1 month prior to the first study visit, throughout the study which averages around 4 months, and monitored for up to 2 months after the final visit.

Secondary Outcomes (2)

• LIFU induced network change based on fMRI and/or electrophysiology

  Obtained at the baseline visit and the final day of serial stimulation, which averages around 4 months.

• Cognitive battery

  The cognitive battery will be performed at baseline visit, as well as at the beginning and end of routine study visits; the duration averages around a 4 month period.

Study Arms (2)

Target optimization using LIFU

ACTIVE COMPARATOR

Participants in this single experimental group will undergo a series of LIFU sessions to determine optimal clinical response. Each participant will receive active LIFU stimulation of up to three personalized brain targets. The study utilizes a within-subject, sham-controlled design where participants receive both active LIFU and sham (placebo) stimulation across different sessions to compare physiological and clinical responses.

Device: Target optimization using LIFU

Serial LIFU stimulation

ACTIVE COMPARATOR

If an optimal target is identified, patients will undergo serial stimulation of the optimal target.

Device: Serial LIFU stimulation

Interventions

Target optimization using LIFU DEVICE

LIFU will be administered using the ATTN201 wearable device by Attune Neurosciences Inc. Positioning is guided by an offline MRI scan, enabling non-invasive targeting of the LIFU beams directly to deep brain structures. Targeting will be determined based on the epileptogenic network.

Also known as: Low Intensity Focused Ultrasound (LIFU)

Target optimization using LIFU

Serial LIFU stimulation DEVICE

Serial LIFU will again be administered using the ATTN201 wearable device by Attune Neurosciences Inc. Serial stimulation target selection will be based on the initial target optimization outcome, including the assessment of physiology and clinical treatment response.

Also known as: Low Intensity Focused Ultrasound (LIFU)

Serial LIFU stimulation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 21 and 65 years of age at screening
• Clinical diagnosis of drug-resistant epilepsy with on average, 4 or more seizures per month.
• Able to provide informed consent (or assent when applicable) by the subject or subject's legal representative.
• Be willing to undergo a brain MRI.
• Be able and willing to wear a headband during the treatment duration.
• Be able to complete scheduled visits and daily seizure logs.

You may not qualify if:

• Has a craniotomy or pathologic intracranial lesion (e.g. vascular malformations) in the trajectory of the focused ultrasound beam.
• Pregnant, breastfeeding, is attempting pregnancy, or unwilling to practice birth control during participation in the study.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Has any unstable medical or psychiatric disease.
• Any contraindications for completing a brain MRI scan.
• Has evidence of any other clinically relevant neurological disorder at the time of screening, including Alzheimer's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Attune Neurosciences Inc: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94107, United States

RECRUITING

Related Publications (1)

• Fan JM, Woodworth K, Murphy KR, Hinkley L, Cohen JL, Yoshimura J, Choi I, Tremblay-McGaw AG, Mergenthaler J, Good CH, Pellionisz PA, Lee AM, Di Ianni T, Sugrue LP, Krystal AD. Thalamic transcranial ultrasound stimulation in treatment resistant depression. Brain Stimul. 2024 Sep-Oct;17(5):1001-1004. doi: 10.1016/j.brs.2024.08.006. Epub 2024 Aug 22. No abstract available.

  PMID: 39173737 BACKGROUND

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy; Epilepsy, Generalized; Epilepsies, Partial; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Joline M Fan, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

4155087069; lifu.research@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants in this single experimental group will undergo a series of low-intensity focused ultrasound (LIFU) sessions to evaluate safety, tolerability, and preliminary efficacy. The study utilizes a within-subject, sham-controlled design where participants receive both active LIFU and sham (placebo) stimulation across different sessions to compare clinical response. Active LIFU stimulation sessions will assess up to three targets relevant to the epileptogenic network. If an optimal target is identified, patients will then undergo serial stimulation of the optimal target.

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: July 2, 2026
• Study Start: July 9, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)