Personalized Ultrasonic Brain Stimulation for Depression (R61)

Personalized Ultrasonic Brain Stimulation for Depression: A Study of Target Engagement and Mood Effects

This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will be delivered using a range of stimulation parameters during psychological and physiological monitoring. Individualized optimal targets will be selected using structural MRI and diffusion tractography. Brain target engagement will be evaluated using functional MRI.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Episode; Depression - Major Depressive Disorder; Treatment-Resistant Major Depressive Disorder
• Intervention / Treatment: Device: LTFUS to SCC; Device: LTFUS to ALIC

Detailed Description

This R61 project has 3 aims:

1. To determine whether stimulation engages the subcallosal cingulate (SCC) in an intensity-dependent manner
2. To examine the degree of specificity of neuromodulation by contrasting the neural effects of stimulating two spatially distinct targets versus sham
3. To evaluate safety, tolerability, and side effects

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Brian J Mickey; Phone Number: 801-587-0159; Email: brian.mickey@utah.deu
• Study Contact Backup: Name: Sarah Kwon; Phone Number: 801-829-7382; Email: utah.depression.research@gmail.com

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Recruiting
      • University of Utah
      • Contact: Angela Valentina Bisconti; Phone Number: 801-587-8972; Email: angelavalentina.bisconti@utah.edu
      • Contact: Brian J Mickey; Phone Number: 801-587-0159; Email: brian.mickey@utah.edu
      • Principal Investigator: Brian J Mickey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-65, any gender.
2. Primary diagnosis of DMS-5 major depressive disorder (MINI).
3. Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months (MINI).
4. Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10.
5. History of at least 2 failed trials of evidence-based antidepressant medication and/or psychotherapy (at least one trial during the current depressive episode).
6. Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study.
7. For participants of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study.
8. Capacity to provide informed consent; provision of a signed and dated consent form
9. Currently are under the care of a licensed psychiatrist or other mental health care provider, or a licensed addiction medicine specialist and agrees to promptly inform the investigator or the study staff of any change in these providers.
10. Agrees to allow any and all forms of communication between the investigators/study staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within at least two years of study enrollment for the purposes of eligibility confirmation or in case of a safety event.
11. Agrees to provide the name and verifiable contact information (email and mailing addresses, mobile and land-line phone numbers, as applicable) of at least two persons 22 years or older who reside within a 60-minute drive of the patient's residence. Subject agrees that in the event of a safety concern or event during study participation, research staff is at liberty to contact these individuals if the subject does not respond to contact attempts.

Exclusion Criteria:

1. History of serious brain injury or other neurologic disorder.
2. Poorly managed general medical condition.
3. Pregnant or breast feeding.
4. Implanted device in the head or neck.
5. MRI intolerance or contraindication.
6. Brain stimulation treatment such as ECT, TMS, or VNS (past month).
7. Recent change in antidepressant treatments (past month).
8. 8. Moderate-High Risk of Suicide according to the Columbia - Suicide Severity Rating Scale (C-SSRS) Screen Version - Recent (answers YES to Question 3 and NO to Question 6 (Moderate risk) or YES to Question 4, 5, or 6 (High risk)) and/or in the clinical judgement of the PI or a study psychiatrist
9. Suicidal behavior (past year).
10. Serious suicide attempt 33 (lifetime).
11. Moderate-to-severe substance use disorder (MINI, past 3 months).
12. Obsessive compulsive disorder, primary diagnosis (MINI, past month).
13. Posttraumatic stress disorder, primary diagnosis (MINI, past month).
14. Bipolar-spectrum disorder (MINI, lifetime).
15. Schizophrenia-spectrum disorder (MINI, lifetime).
16. Neurocognitive disorder (DSM-5, past year).
17. Severe personality disorder.
18. Clinically inappropriate for participation in the study as determined by the study team.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: SCC-ALIC; Low-intensity transcranial focused ultrasound stimulation (LTFUS) is delivered to the subgenual cingulate cortex (SCC) at the first stimulation visit, then LTFUS is delivered to the anterior limb of the internal capsule (ALIC) at the second stimulation visit.	Device: LTFUS to SCC; Low-intensity transcranial focused ultrasound delivered to subgenual cingulate cortex; Device: LTFUS to ALIC; Low-intensity transcranial focused ultrasound delivered to anterior limb of internal capsule
Experimental: Group 2: ALIC-SCC; Low-intensity transcranial focused ultrasound stimulation (LTFUS) is delivered to the anterior limb of the internal capsule (ALIC) at the first stimulation visit, then LTFUS is delivered to the subgenual cingulate cortex (SCC) at the second stimulation visit.	Device: LTFUS to SCC; Low-intensity transcranial focused ultrasound delivered to subgenual cingulate cortex; Device: LTFUS to ALIC; Low-intensity transcranial focused ultrasound delivered to anterior limb of internal capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modulation of SCC activity during SCC stimulation	Functional MRI is used to quantify modulation of SCC activity during SCC stimulation	Days 14, 21, 28
Modulation of SCC activity during ALIC stimulation	Functional MRI is used to quantify modulation of SCC activity during ALIC stimulation	Days 14, 21
Study dropout	Dropout or withdrawal due to stimulation-related adverse effects	From enrollment to the end of participation at 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANAS-X	Positive and Negative Affect Schedule, Expanded Form	Immediately before and after each LTFUS on Days 14, 21, 28
MADRS	Montgomery-Asberg Depression Rating Scale	Days 14, 21, 28, 35, 49
HDRS-6	6-item Hamilton Depression Rating Scale	Days 0, 14, 15, 21, 22, 28, 29, 35, 49
IDS-SR	Inventory of Depressive Symptomatology, Self-Rated	Days 0, 14, 21, 28, 35, 49
GAD-7	7-item Generalized Anxiety Disorder Scale	Days 0, 14, 21, 28, 35, 49
YMRS	Young Mania Rating Scale	Days 0, 14, 15, 21, 22, 28, 29, 35, 49
C-SSRS	Columbia Suicide Severity Rating Scale, Screen Version	Days 0, 14, 15, 21, 22, 28, 29, 35, 49
GASE	Generic Assessment of Side Effects scale	Days 15, 22, 29
MoCA	Montreal Cognitive Assessment	Days 14, 15, 49

Collaborators and Investigators

• Sponsor: Brian Mickey
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Brian J Mickey, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: low-intensity focused ultrasound; ultrasonic neuromodulation
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: IRB_00148802R61; R61MH134943 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No