Focused Ultrasound Amygdala Neuromodulation

NCT05228964 | Completed FDA Device

• 1 other identifier: STUDY00000137
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to examine the feasibility and potential efficacy of low-intensity focused ultrasound as a method of modulating amygdala function to promote improvements in symptoms of an affective disorder. Ultrasound is frequently and safely utilized for diagnostic purposes. In this study, the investigators will utilize magnetic resonance imaging (MRI) and neuronavigation to target the left amygdala and apply ultrasound. This will be conducted once a day, 5 days a week, for 3 weeks. This will be an open-label, single-arm trial.

Conditions

Bipolar Depression; Depression; Anxiety Disorders; Ptsd

Keywords

amygdala; focused ultrasound; neuromodulation; affective disorder; fMRI

Outcome Measures

Primary Outcomes (3)

• Change from Baseline on the 30 item Mood and Anxiety Symptom Questionnaire General Distress Subscale score at 6 weeks

  A measure of general distress related to mood and anxiety symptoms. Scores range from 10-50, with lower scores indicating less symptoms.

  Through study completion, around 6 weeks

• Change from Baseline fMRI activation to emotional stimuli at 6 weeks

  Task-based brain activation to emotional faces

  Through study completion, around 6 weeks

• Change from Baseline fMRI resting state connectivity at 6 weeks

  Connectivity between the left amygdala and the rest of the brain

  Through study completion, around 6 weeks

Secondary Outcomes (20)

• Change from Baseline Spielberger State-Trait Anxiety Inventory score at 6 weeks

  Through study completion, around 6 weeks

• Change from Baseline PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders 5th Edition score at 6 weeks

  Through study completion, around 6 weeks

• Change from Baseline Snaith Hamilton Pleasure Scale at 6 weeks

  Through study completion, around 6 weeks

• Change from Baseline Quick Inventory of Depressive Symptom Self-Report score at 6 weeks

  Through study completion, around 6 weeks

• Change from Baseline World Health Organization Quality of Life Inventory-Brief subscale scores at 6 weeks

  Through study completion, around 6 weeks

Study Arms (1)

Open-label focused ultrasound

EXPERIMENTAL

Focused ultrasound at a 10 Hz pulse repetition frequency, 5% duty cycle, and 720 mw/cm squared de-rated spatial peak temporal average intensity, delivered over 10 min once a day, five days a week for 3 weeks.

Device: Focused ultrasound

Interventions

Focused ultrasound DEVICE

Focused ultrasound at a 10 Hz pulse repetition frequency, 5% duty cycle, and 720 mw/cm squared de-rated spatial peak temporal average intensity, delivered over 10 min.

Open-label focused ultrasound

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ages 18-65
• Willing and able to undergo the MRI and LIFUP procedures and repeated LIFUP for up to 15 sessions
• English language proficiency sufficient to speak to investigators and understand investigator instruction
• Can visit the laboratory several times over the course of 2 to 6 weeks
• Individuals with a primary affective disorder diagnosis (major depression, bipolar disorder, an anxiety disorder, or posttraumatic stress disorder on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Diagnosis 5th Edition
• Score of 19 or greater on the general distress subscale of the 30-item Mood and Anxiety Symptom Questionnaire
• Psychiatric medication(s) on a stable dosage and regimen for the past 3 months (including antidepressants, mood stabilizers, atypical antipsychotics, and sedatives/hypnotics)

You may not qualify if:

• Contraindications to LIFUP or MRI including, but not limited to, history of stroke, brain tumors, brain hemorrhages, internal wires, electrodes, pacemakers, implants, irremovable ferromagnetic objects in head that are unsafe for MRI and/or cause large distortions in imaging data, history of seizures (except febrile seizures in childhood), brain surgery, moderate-to-severe head injury or any penetrating head injury, and uncontrolled thyroid disorder.
• Pregnant women or people trying to become pregnant will also be excluded due to the unknown effects of MRI on developing fetuses
• Individuals with serious medical illnesses that are likely to interfere with study: cancer, autism, narcolepsy etc.
• Current active suicidal/homicidal ideation (or suicide attempt in the past 3 months)
• Current substance-use disorder
• Current or recent (within 3 months) psychotic symptoms, or currently meeting diagnostic criteria for a manic episode
• Individuals currently actively engaged in evidence-based or experimental treatments (e.g., weekly cognitive behavioral psychotherapies, transcranial magnetic stimulation, ketamine/esketamine treatment) other than psychiatric medication(s)

Sponsors & Collaborators

• University of Texas at Austin: lead

Study Sites (1)

Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600

Austin, Texas, 78712, United States

Location

Related Publications (1)

• Barksdale BR, Enten L, DeMarco A, Kline R, Doss MK, Nemeroff CB, Fonzo GA. Low-intensity transcranial focused ultrasound amygdala neuromodulation: a double-blind sham-controlled target engagement study and unblinded single-arm clinical trial. Mol Psychiatry. 2025 Oct;30(10):4497-4511. doi: 10.1038/s41380-025-03033-w. Epub 2025 Apr 24.

  PMID: 40275098 DERIVED

MeSH Terms

Conditions

Depression; Anxiety Disorders; Bipolar Disorder; Stress Disorders, Post-Traumatic; Mood Disorders

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Bipolar and Related Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Study Officials

• Gregory A Fonzo, Ph.D.

  The University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single arm, open-label

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 8, 2022
• Study Start: January 13, 2022
• Primary Completion: October 1, 2024
• Study Completion: April 27, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)