Drug-Resistant Epilepsy, Epilepsy, Epilepsy Comorbidities, Epilepsy, Drug Resistant, Epilepsy, Focal, Epilepsy, Generalized, Epilepsy (Treatment Refractory)
Conditions
Keywords
Seizures, Drug-Resistant Epilepsy, Epilepsy, Transcranial Ultrasound Stimulation, Focused ultrasound Stimulation, Electroencephalography (EEG), Low Intensity Focused ultrasound (LIFU)
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.
Interventions
DEVICETarget optimization using LIFU
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.
DEVICESerial LIFU stimulation
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.
Sponsors
University of California, San Francisco
Attune Neurosciences Inc
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Frequency | 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. | Seizure counts will be obtained from a seizure diary kept by each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | 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). |
Countries
United States
Contacts
CONTACTStudy Coordinator
PRINCIPAL_INVESTIGATORJoline M Fan, MD, MS
University of California, San Francisco
Outcome results
None listed