Post-traumatic Brain Injury DepressionNCT07828483
Development of Low-Intensity Focused Ultrasound for Post Traumatic Brain Injury Depression
A study testing Active Low-Intensity Focused Ultrasound (LIFU) in people with Post-traumatic Brain Injury Depression and Veteran Health, run by Stanford University at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn about evaluate the safety, tolerability, and feasibility of MRI-guided LIFU targeting the sgACC in Veterans with post-traumatic brain injury depression. The main questions it aims to answer are: 1. the safety, tolerability, and feasibility of MRI-guided LIFU. 2. Read more about this study
- Who is it for?
- Ages 22 to 55 years
- Conditions the study is for
- Post-traumatic Brain Injury Depression, Veteran Health
- What is being tested?
- Active Low-Intensity Focused Ultrasound (LIFU)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 31 Dec 2028
- Phase
- Interventional
- 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 22 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adult Veteran, male or female, 22 to 55 years of age at the time of screening.
- Able to read, understand, and provide written, dated informed consent before initiation of formal study screening procedures. A brief IRB-approved telephone pre-screen may be conducted prior to written informed consent as described in Section 8.1. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and LIFU interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- History of non-penetrating mild to moderate TBI confirmed by medical records and adjudicated by the study investigator using established TBI criteria (e.g., ACRM/VA-DoD criteria). If contemporaneous records are incomplete, a structured lifetime TBI interview may be used to support classification.
- The TBI must have occurred at least 3 months before the occurrence of depression
- Current depressive disorder defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM3).
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- MADRS score of ≥20 at screening.
- Total duration of current depressive episode is less than 2 years
- LIFU naive.
- Access to ongoing psychiatric care before and after completion of the study.
- The dose of the primary antidepressant medication must be stable for 6 weeks prior to baseline , and participants must agree to continue at this dose throughout the study period.
- In good general health, as evidenced by medical history.
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to baseline and agreement to use such a method during study participation.
- Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration.
Who cannot join
- Any lifetime DSM-5 depressive disorder or clinically significant depressive episode with onset prior to the qualifying index TBI, including major depressive disorder, persistent depressive disorder, or other specified/unspecified depressive disorder, or any antidepressant treatment initiated for depression prior to the index TBI.
- Pregnancy
- Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
- History of or current psychotic disorder or bipolar disorder
- Severe borderline personality disorder.
- Diagnosis of Intellectual Disability or Autism Spectrum Disorder
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- Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
- Urine screening test positive for illicit substances
- Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt (as defined by the C-SSRS) within the past one year
- Cognitive impairment (defined as MoCA < 23)
- 10. Any history of ECT without meeting responder criteria 11. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) 12. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, or multiple sclerosis 13. Untreated or insufficiently treated endocrine disorder. 14. Contraindication to receiving LIFU 15. Contraindication to MRI (ferromagnetic metal in their body) 16. Treatment with another investigational drug or other intervention within the study period 17. Unstable symptoms between screening and baseline as defined by a > 30% change in MADRS-S score.
- 18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
John P Coetzee, PhD contact
United States1 site
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, California, 94305
Nick Bassano, MSW, 6504973933, nbassano@stanford.edu
Mahendra Bhati, MD
About this study
The goal of this clinical trial is to learn about evaluate the safety, tolerability, and feasibility of MRI-guided LIFU targeting the sgACC in Veterans with post-traumatic brain injury depression. The main questions it aims to answer are:
- the safety, tolerability, and feasibility of MRI-guided LIFU.
- Evaluate preliminary antidepressant efficacy.
- Characterize target engagement using multimodal neuroimaging and electrophysiology.
- Identify imaging and electrophysiological biomarkers that predict treatment response.
- Generate preliminary effect size estimates to support future multicenter clinical trials.
Read the detailed description
The study is a single-site, randomized (3:2 to active LIFU or sham), rater- and participant-blinded mechanistic study of MRI-guided low-intensity focused ultrasound (LI-FUS) targeting the subgenual anterior cingulate cortex (sgACC) in adult Veterans with post traumatic brain injury depression (PTD). The purpose of this study is to evaluate the safety and tolerability of repeated sgACC-targeted LI-FUS stimulation in adult Veterans with PTD. To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LI-FUS in adult Veterans with PTD. To characterize the relationship between delivered LI-FUS dose and clinical response in adult Veterans with PTD. To characterize changes in neuroimaging and electrophysiologic measures associated with LI-FUS, including fMRI- and EEG-based indices of target engagement and network modulation, in adult Veterans with PTD. (b) To evaluate whether baseline fMRI and EEG features predict clinical response to LI-FUS in adult Veterans with PTD.
- Being tested
- Active Low-Intensity Focused Ultrasound (LIFU), Sham Low-Intensity Focused Ultrasound (LIFU)
- Keywords
- post-traumatic brain injury, depression, veteran
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Low-Intensity Focused Ultrasound (LIFU)Device
MRI-guided Low-Intensity Focused Ultrasound (LIFU) neuromodulation targeting the sgACC delivered over a brief, intensive course (20-minute sessions; 5 sessions/day for 5 consecutive days).
Sham Low-Intensity Focused Ultrasound (LIFU)Other
Non-active MRI-guided Low-Intensity Focused Ultrasound (LIFU) neuromodulation targeting the sgACC delivered over a brief, intensive course (20-minute sessions; 5 sessions/day for 5 consecutive days).
| Study group | Role | What they receive |
|---|---|---|
| Active Low-Intensity Focused Ultrasound (LIFU) | Active comparator | Participants receive active LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session Receives: Device: Active Low-Intensity Focused Ultrasound (LIFU) |
| Sham Low-Intensity Focused Ultrasound (LIFU) | Sham comparator | Participants receive sham LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session Receives: Other: Sham Low-Intensity Focused Ultrasound (LIFU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of repeated sgACC-targeted LIFU stimulation in adult Veterans with PTD.
Cumulative incidence of treatment-emergent adverse events and serious adverse events.
Measured: Baseline, Treatment Days 1 through 5, 1-Week, 1-2:4-week follow up visits.
Secondary outcomes (1)
To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LIFU in adult Veterans with PTD.
Absolute change from baseline in the MADRS total score.
Measured: Baseline, 1-week follow up, 4-week follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-traumatic Brain Injury DepressionStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Palo Alto Health Care System
- Responsible party
- Principal investigator, Mahendra Bhati, Stanford University
- Investigators
- Mahendra Bhati, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07828483
- Sponsor's protocol ID
- 85834
- Status last verified
- Sep 2026
- First submitted
- 14 Sep 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Low-Intensity Focused Ultrasound for Post Traumatic Brain Injury Depression
- ClinicalTrials.gov ID
- NCT07828483
- Acronym / sponsor ID
- 85834
- Keywords
- post-traumatic brain injury, depression, veteran
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- VA Palo Alto Health Care System
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 18 Sep 2026 (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.
The goal of this clinical trial is to learn about evaluate the safety, tolerability, and feasibility of MRI-guided LIFU targeting the sgACC in Veterans with post-traumatic brain injury depression. The main questions it aims to answer are:
- the safety, tolerability, and feasibility of MRI-guided LIFU.
- Evaluate preliminary antidepressant efficacy.
- Characterize target engagement using multimodal neuroimaging and electrophysiology.
- Identify imaging and electrophysiological biomarkers that predict treatment response.
- Generate preliminary effect size estimates to support future multicenter clinical trials.
Detailed description
The study is a single-site, randomized (3:2 to active LIFU or sham), rater- and participant-blinded mechanistic study of MRI-guided low-intensity focused ultrasound (LI-FUS) targeting the subgenual anterior cingulate cortex (sgACC) in adult Veterans with post traumatic brain injury depression (PTD). The purpose of this study is to evaluate the safety and tolerability of repeated sgACC-targeted LI-FUS stimulation in adult Veterans with PTD. To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LI-FUS in adult Veterans with PTD. To characterize the relationship between delivered LI-FUS dose and clinical response in adult Veterans with PTD. To characterize changes in neuroimaging and electrophysiologic measures associated with LI-FUS, including fMRI- and EEG-based indices of target engagement and network modulation, in adult Veterans with PTD. (b) To evaluate whether baseline fMRI and EEG features predict clinical response to LI-FUS in adult Veterans with PTD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Low-Intensity Focused Ultrasound (LIFU) | Active comparator | Device: Active Low-Intensity Focused Ultrasound (LIFU)Participants receive active LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session |
| Sham Low-Intensity Focused Ultrasound (LIFU) | Sham comparator | Other: Sham Low-Intensity Focused Ultrasound (LIFU)Participants receive sham LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session |
Who may qualify
- Ages
- 22 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Adult Veteran, male or female, 22 to 55 years of age at the time of screening.
- Able to read, understand, and provide written, dated informed consent before initiation of formal study screening procedures. A brief IRB-approved telephone pre-screen may be conducted prior to written informed consent as described in Section 8.1. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and LIFU interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- History of non-penetrating mild to moderate TBI confirmed by medical records and adjudicated by the study investigator using established TBI criteria (e.g., ACRM/VA-DoD criteria). If contemporaneous records are incomplete, a structured lifetime TBI interview may be used to support classification.
- The TBI must have occurred at least 3 months before the occurrence of depression
- Current depressive disorder defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
Key exclusion criteria (12 listed)
- Any lifetime DSM-5 depressive disorder or clinically significant depressive episode with onset prior to the qualifying index TBI, including major depressive disorder, persistent depressive disorder, or other specified/unspecified depressive disorder, or any antidepressant treatment initiated for depression prior to the index TBI.
- Pregnancy
- Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
- History of or current psychotic disorder or bipolar disorder
- Severe borderline personality disorder.
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 |
|---|---|---|
| Active Low-Intensity Focused Ultrasound (LIFU)MRI-guided Low-Intensity Focused Ultrasound (LIFU) neuromodulation targeting the sgACC delivered over a brief, intensive course (20-minute sessions; 5 sessions/day for 5 consecutive days). | Device | Active Low-Intensity Focused Ultrasound (LIFU) |
| Sham Low-Intensity Focused Ultrasound (LIFU)Non-active MRI-guided Low-Intensity Focused Ultrasound (LIFU) neuromodulation targeting the sgACC delivered over a brief, intensive course (20-minute sessions; 5 sessions/day for 5 consecutive days). | Other | Sham Low-Intensity Focused Ultrasound (LIFU) |
Primary outcome
To evaluate the safety and tolerability of repeated sgACC-targeted LIFU stimulation in adult Veterans with PTD.
Time frame: Baseline, Treatment Days 1 through 5, 1-Week, 1-2:4-week follow up visits.
Cumulative incidence of treatment-emergent adverse events and serious adverse events.
1 secondary outcome
To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LIFU in adult Veterans with PTD.
Time frame: Baseline, 1-week follow up, 4-week follow up
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 18 Sep 2026.
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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.
John P Coetzee, PhD contact
Mahendra Bhati, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Low-Intensity Focused Ultrasound (LIFU) in people with Post-traumatic Brain Injury Depression and Veteran Health, run by Stanford University 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 14 inclusion and 12 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: opening soon, as of the sponsor's last update on 18 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Contact Masataka Wada, MD (650-434-7844, mwada@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety and tolerability of repeated sgACC-targeted LIFU stimulation in adult Veterans with PTD. (time frame: Baseline, Treatment Days 1 through 5, 1-Week, 1-2:4-week follow up visits.). 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 18 Sep 2026.