Major Depressive EpisodePhase 1/2NCT06902298
Personalized Ultrasonic Brain Stimulation for Depression (R61)
A Phase 1/2 study testing LTFUS to SCC and LTFUS to ALIC in people with Major Depressive Episode and Depression - Major Depressive Disorder, run by Brian Mickey at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Episode, Depression - Major Depressive Disorder, Treatment-Resistant Major Depressive Disorder
- What is being tested?
- LTFUS to SCC and LTFUS to ALIC
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2025to 11 Sep 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65, any gender.
- Primary diagnosis of DMS-5 major depressive disorder (MINI).
- Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months (MINI).
- Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10.
- History of at least 2 failed trials of evidence-based antidepressant medication and/or psychotherapy (at least one trial during the current depressive episode).
- Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study.
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- 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.
- Capacity to provide informed consent; provision of a signed and dated consent form
- 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.
- 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.
- 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.
Who cannot join
- History of serious brain injury or other neurologic disorder.
- Poorly managed general medical condition.
- Pregnant or breast feeding.
- Implanted device in the head or neck.
- MRI intolerance or contraindication.
- Brain stimulation treatment such as ECT, TMS, or VNS (past month).
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- Recent change in antidepressant treatments (past month).
- 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
- Suicidal behavior (past year).
- Serious suicide attempt 33 (lifetime).
- Moderate-to-severe substance use disorder (MINI, past 3 months).
- Obsessive compulsive disorder, primary diagnosis (MINI, past month).
- Posttraumatic stress disorder, primary diagnosis (MINI, past month).
- Bipolar-spectrum disorder (MINI, lifetime).
- Schizophrenia-spectrum disorder (MINI, lifetime).
- Neurocognitive disorder (DSM-5, past year).
- Severe personality disorder.
- Clinically inappropriate for participation in the study as determined by the study team.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
This R61 project has 3 aims:
- To determine whether stimulation engages the subcallosal cingulate (SCC) in an intensity-dependent manner
- To examine the degree of specificity of neuromodulation by contrasting the neural effects of stimulating two spatially distinct targets versus sham
- To evaluate safety, tolerability, and side effects
- Conditions
- Major Depressive Episode, Depression - Major Depressive Disorder, Treatment-Resistant Major Depressive Disorder
- Being tested
- LTFUS to SCC, LTFUS to ALIC
- Keywords
- ultrasonic neuromodulation, low-intensity focused ultrasound
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LTFUS to SCCDevice
Low-intensity transcranial focused ultrasound delivered to subgenual cingulate cortex
LTFUS to ALICDevice
Low-intensity transcranial focused ultrasound delivered to anterior limb of internal capsule
| Study group | Role | What they receive |
|---|---|---|
| Group 1: SCC-ALIC | Experimental | 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. Receives: Device: LTFUS to SCC; Device: LTFUS to ALIC |
| Group 2: ALIC-SCC | Experimental | 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. Receives: Device: LTFUS to SCC; Device: LTFUS to ALIC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modulation of SCC activity during SCC stimulation
Functional MRI is used to quantify modulation of SCC activity during SCC stimulation
Measured: Days 14, 21, 28
Modulation of SCC activity during ALIC stimulation
Functional MRI is used to quantify modulation of SCC activity during ALIC stimulation
Measured: Days 14, 21
Study dropout
Dropout or withdrawal due to stimulation-related adverse effects
Measured: From enrollment to the end of participation at 7 weeks
Secondary outcomes (9)
PANAS-X
Positive and Negative Affect Schedule, Expanded Form
Measured: Immediately before and after each LTFUS on Days 14, 21, 28
MADRS
Montgomery-Asberg Depression Rating Scale
Measured: Days 14, 21, 28, 35, 49
HDRS-6
6-item Hamilton Depression Rating Scale
Measured: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
IDS-SR
Inventory of Depressive Symptomatology, Self-Rated
Measured: Days 0, 14, 21, 28, 35, 49
GAD-7
7-item Generalized Anxiety Disorder Scale
Measured: Days 0, 14, 21, 28, 35, 49
YMRS
Young Mania Rating Scale
Measured: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
C-SSRS
Columbia Suicide Severity Rating Scale, Screen Version
Measured: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
GASE
Generic Assessment of Side Effects scale
Measured: Days 15, 22, 29
MoCA
Montreal Cognitive Assessment
Measured: Days 14, 15, 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2025
- Study start10 Mar 2025
- Primary completion11 Sep 2026 (estimated)
- Study completion11 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive EpisodeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Two brain targets will be stimulated sequentially. The order of the two targets will be randomized.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brian Mickey
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Brian Mickey, University of Utah
- Investigators
- Brian J Mickey, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06902298
- Sponsor's protocol ID
- IRB_00148802R61
- Other IDs
- R61MH134943
- Status last verified
- Sep 2026
- First submitted
- 24 Mar 2025
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Ultrasonic Brain Stimulation for Depression: A Study of Target Engagement and Mood Effects
- ClinicalTrials.gov ID
- NCT06902298
- Acronym / sponsor ID
- IRB_00148802R61
- Conditions
- Major Depressive Episode, Depression - Major Depressive Disorder, Treatment-Resistant Major Depressive Disorder
- Keywords
- ultrasonic neuromodulation, low-intensity focused ultrasound
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Brian MickeyUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 10 Mar 2025 (actual)
- Primary completion
- 11 Sep 2026 (estimated)
- Study completion
- 11 Sep 2026 (estimated)
- First posted
- 30 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This R61 project has 3 aims:
- To determine whether stimulation engages the subcallosal cingulate (SCC) in an intensity-dependent manner
- To examine the degree of specificity of neuromodulation by contrasting the neural effects of stimulating two spatially distinct targets versus sham
- To evaluate safety, tolerability, and side effects
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two brain targets will be stimulated sequentially. The order of the two targets will be randomized.
| Arm | Type | Receives |
|---|---|---|
| Group 1: SCC-ALIC | Experimental | Device: LTFUS to SCC, Device: LTFUS to ALICLow-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. |
| Group 2: ALIC-SCC | Experimental | Device: LTFUS to SCC, Device: LTFUS to ALICLow-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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18-65, any gender.
- Primary diagnosis of DMS-5 major depressive disorder (MINI).
- Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months (MINI).
- Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10.
- History of at least 2 failed trials of evidence-based antidepressant medication and/or psychotherapy (at least one trial during the current depressive episode).
Key exclusion criteria (18 listed)
- History of serious brain injury or other neurologic disorder.
- Poorly managed general medical condition.
- Pregnant or breast feeding.
- Implanted device in the head or neck.
- MRI intolerance or contraindication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LTFUS to SCCLow-intensity transcranial focused ultrasound delivered to subgenual cingulate cortex | Device | Group 1: SCC-ALIC, Group 2: ALIC-SCC |
| LTFUS to ALICLow-intensity transcranial focused ultrasound delivered to anterior limb of internal capsule | Device | Group 1: SCC-ALIC, Group 2: ALIC-SCC |
Primary outcome
Modulation of SCC activity during SCC stimulation
Time frame: Days 14, 21, 28
Functional MRI is used to quantify modulation of SCC activity during SCC stimulation
Modulation of SCC activity during ALIC stimulation
Time frame: Days 14, 21
Functional MRI is used to quantify modulation of SCC activity during ALIC stimulation
Study dropout
Time frame: From enrollment to the end of participation at 7 weeks
Dropout or withdrawal due to stimulation-related adverse effects
9 secondary outcomes
PANAS-X
Time frame: Immediately before and after each LTFUS on Days 14, 21, 28
MADRS
Time frame: Days 14, 21, 28, 35, 49
HDRS-6
Time frame: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
IDS-SR
Time frame: Days 0, 14, 21, 28, 35, 49
GAD-7
Time frame: Days 0, 14, 21, 28, 35, 49
YMRS
Time frame: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
C-SSRS
Time frame: Days 0, 14, 15, 21, 22, 28, 29, 35, 49
GASE
Time frame: Days 15, 22, 29
MoCA
Time frame: Days 14, 15, 49
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian J Mickey principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LTFUS to SCC and LTFUS to ALIC in people with Major Depressive Episode and Depression - Major Depressive Disorder, run by Brian Mickey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modulation of SCC activity during SCC stimulation (time frame: Days 14, 21, 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.