The Impact of Focused Ultrasound Thalamotomy of the Anterior Nucleus for Focal-Onset Epilepsy on Anxiety

NCT05032105 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 2023H0325
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the feasibility, safety, and effects on anxiety of high intensity focused ultrasound ablation (FUSA) in patients suffering from treatment-refractory focal epilepsy and anxiety. FUSA is a non-invasive neurosurgical procedure that uses ultrasound waves, sent directly through the scalp and skull, to precisely target small abnormal areas of the brain. For this study, the targeted area of the brain is the anterior nucleus of the thalamus. This brain region may cause seizures and may also be involved in anxiety. The study will test if FUSA is safe and tolerated, and if it reduces anxiety and brain response to threat in patients with anxiety receiving the procedure for partial-onset epilepsy that is resistant to medications.

Conditions

Anxiety; Medication-refractory Focal-onset Epilepsy

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events

  Safety will be determined by an evaluation of the incidence and severity of MRgFUSA-ATN and other research procedures related adverse events from the 1st study visit through the 12-month post-treatment time point. Post-procedural imaging will be evaluated for evidence of swelling, hemorrhage, and the evolution of the ATN lesion. Emergence of complications will be monitored by neurological examination at day 1, day 7, month 1, month 3, month 6 and month 12 post-procedure. A comprehensive battery of neuropsychological assessments will be conducted by board-certified neuropsychologists at study screening, 3-month and 12-month postoperative time points. All events that are not procedure related will also be captured and recorded.

  12 months

• Target

  Feasibility will be determined by ability to create the desired lesion within the anterior nucleus of the thalamus as assessed by neuroimaging

  1 month

• Change in Anxiety symptoms

  Change in anxiety symptoms will be measured using clinician-administered HAM-A scale before the procedure and at various time points after the procedure. HAM-A is the scale of reference used in clinical trials to rate the severity of symptoms of anxiety in patients. It will be collected before and after the procedure at day 1, 7, months 1, 3, 6 and 12 to determine any effect and its change overtime.

  12 months

• Effect on Threat Reactivity

  Change in Threat reactivity measured by fMRI task just before and after MRgFUSA

  1 day

Secondary Outcomes (6)

• Change in seizure frequency

  12 months

• Ability to perform the threat reactivity fMRI task just before and after MRgFUSA

  4 years

• Change in self-reported anxiety symptoms

  12 months

• Change in self-reported anxiety symptoms

  12 months

• Change in quality of life

  12 months

Study Arms (1)

Intervention

EXPERIMENTAL

Unilateral Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus (ATN)

Device: Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA)

Interventions

Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) DEVICE

Unilateral Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus (ATN)

Intervention

Eligibility Criteria

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

You may qualify if:

• Disabling, medically refractory epilepsy (≥2 anti-epileptic drug failures).
• Focal onset seizures with secondary generalization; with or without primary generalized seizures.
• Previous seizure work-up within 12 months of enrollment date to include:
• A. Home EEG or EMU video EEG or intracranial EEG. B. High definition MRI imaging/PET imaging. C. Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF).
• ≥ 3 seizures/month on average within 3 months of enrollment.
• Stable medication (including anti-epileptic and psychotropic/psychoactive medications) dosage for 3 months before enrollment.
• Moderate-severe anxiety as measured by the Hamilton Anxiety Rating Scale (HAM-A) score \> 17.
• Anterior Nucleus (AN) identifiable on MRI (structural T1 and T2 images).
• Willing to maintain seizure diary (3 months before \& 3 months after).
• Involved care provider.
• Written informed consent to participate.
• Ability to comply with all testing, follow-ups, and study appointments and protocols.

You may not qualify if:

• Low seizure frequency (\<3 seizures/month).
• Generalized epilepsy (Lennox Gastaut, drop attacks).
• Post infectious epilepsy (post herpetic).
• Unable or unwilling to maintain anti-epilepsy drug dosage for 3 months post treatment.
• Active (current in past 12 months), uncontrolled DSM-5 psychiatric disorder, except for anxiety disorders.
• Recent (past 12 months) history of drugs or alcohol abuse as evidenced by diagnosis of Substance Use Disorder.
• Active suicidal ideation current and past 30 days.
• Clinically significant neurological disorder, except for epilepsy.
• Presence of any neurodegenerative disease suspected on neurological examination. These include but are not limited to: Multisystem atrophy; Progressive supranuclear palsy; Dementia with Lewy bodies; Alzheimer's disease; Parkinson's disease.
• Cerebrovascular disease (multiple CVA or CVA within six months).
• Significant structural brain abnormalities.
• Surgical lesion identifiable on imaging.
• Symptoms and signs of increased intracranial pressure.
• Patients with any types of brain tumors, including metastases.
• Previous vagal nerve stimulator.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Kinh Luan Phan, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Timothy Lucas, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Marie Duchemin

CONTACT

614-293-5517; anne-marie.duchemin@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurological Surgery

Model Details: Single arm, open-label, prospective intervention study of MRgFUSA for adults with refractory, partial-onset epilepsy with moderate-severe anxiety

Study Record Dates

• First Submitted: August 21, 2021
• First Posted: September 2, 2021
• Study Start: June 4, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 24, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)