Personalized Ultrasonic Brain Stimulation for Depression

Personalized Ultrasonic Brain Stimulation for Depression: A Pilot 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 first be delivered using a range of stimulation parameters during psychological and physiological monitoring. A well-tolerated stimulation protocol will then be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial to evaluate brain target engagement using magnetic resonance imaging.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Episode
• Intervention / Treatment: Device: Diadem prototype

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-65, any gender
2. Primary diagnosis of major depressive disorder or bipolar disorder
3. Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months
4. Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10
5. Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study
6. For females 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
7. Capacity to provide informed consent; provision of a signed and dated consent form

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 (e.g., ECT, TMS, VNS) in the past month
7. Suicidal ideation (Columbia Suicide Severity Rating Scale screen item #2, past month)
8. Lifetime history of a serious suicide attempt
9. Moderate-to-severe substance use disorder (past 3 months)
10. Obsessive compulsive disorder (past month)
11. Posttraumatic stress disorder (past month)
12. Schizophrenia-spectrum disorder (lifetime)
13. Neurocognitive disorder (past year)
14. Personality disorder as a current focus of treatment
15. Clinically inappropriate for participation in the study as determined by the study team

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active stimulation; Personalized low-intensity transcranial focused ultrasound stimulation of deep brain target (subgenual cingulate or alternative targets)	Device: Diadem prototype; Diadem prototype device delivers personalized low-intensity transcranial focused ultrasound stimulation
Sham Comparator: Sham stimulation; Personalized low-intensity transcranial focused ultrasound stimulation of lateral ventricle	Device: Diadem prototype; Diadem prototype device delivers personalized low-intensity transcranial focused ultrasound stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target engagement: MRI quantification of brain activation	Blood oxygenation level dependent (BOLD) or arterial spin labeling (ASL) response to active versus sham stimulation	1 day at MRI study visit
Target engagement: MRI quantification of brain connectivity	Resting functional connectivity of target in response to active versus sham stimulation	1 day at MRI study visit
Change in depression severity measured with the HDRS-6	6-item Hamilton Depression Rating Scale (HDRS-6), range 0-22, higher score represents greater depression	1 day and 7 days after stimulation
Change in Sadness scale of PANAS-X	Positive and Negative Affect Schedule Extended (PANAS-X), range 0-100, higher score represents greater sadness	1 hour, at stimulation study visit

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Brian J Mickey, MD, PhD, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): July 14, 2024
• Study Completion (Estimated): December 14, 2024

Study Registration Dates

• First Submitted: March 20, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: IRB_00148802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No