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

University of California, San Francisco40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Drug-Resistant Epilepsy Epilepsy Epilepsy (Treatment Refractory)Epilepsy Comorbidities Epilepsy, Drug Resistant

Interventions

Target optimization using LIFUDEVICE

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.

Serial LIFU stimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 21 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria * 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. Exclusion Criteria * 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.

Outcomes

Primary Outcomes

Seizure Frequency

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

Time frame: 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

LIFU induced network change based on fMRI and/or electrophysiology

Baseline and post-serial stimulation fMRI and scalp electroencephalogram (EEG) will be obtained and compared. To measure brain activity, individuals will undergo a 1-hour scalp EEG recording with sensors placed in a standard 10-20 montage array. Patients will be instructed to rest quietly and attempt sleep during this routine EEG. EEG outcome measures will include interictal epileptiform discharge frequency and spectral power changes in the delta to gamma frequency bands pre versus post stimulation.

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

Cognitive battery

A cognitive battery will be performed before and following stimulation and will span elements of working memory, inhibition, and planning. The cognitive battery will constitute the N-back (working memory), flanker (inhibition), dimensional set-shifting (set-shifting), and visuospatial memory assessments (working spatial memory).

Time frame: 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.