DepressionLIFUNCT05147142
Low Intensity Focused Ultrasound: a New Paradigm for Depression and Anxiety
A study testing Low Intensity Focused Ultrasound in people with Depression, run by Ocean State Research Institute, Inc. at 1 site in United States.
Trial summary
Objective: Preliminary studies show that low intensity focused ultrasound (LIFU), a new type of non invasive brain stimulation, may be able to reach deep structures of the brain involved with depression and anxiety, that remain inaccessible using current forms of non-invasive brain stimulation with precision. Read more about this study
- Who is it for?
- Ages 22 to 75 years
- Conditions the study is for
- Depression
- What is being tested?
- Low Intensity Focused Ultrasound
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2021to 4 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet DSM-5 criteria for major depressive disorder with and without anxiety symptoms
- Patients must also be symptomatic (i.e. symptom severity above clinical thresholds using standard rating scales) and, if relevant, stable treatment(s) for >6 weeks.
Who cannot join
- history of seizure disorder or serious neurologic illness including dementia
- structural or neurologic abnormalities present or in close proximity to sonication site for patients (e.g., clinically significant calcification as might be observed in Fahr disease)
- history of brain surgery, iv) pacemaker or implanted central nervous system device
- greater than mild traumatic brain injury, or any head injury within sixty days of participation
- greater than moderate alcohol or substance use disorders (last six months; excluding nicotine/caffeine)
- active use or withdrawal from alcohol or substances (assessed via breathalyzer/urine testing as indicated)
Show all 12Show fewer
- metal in the head
- impediment to vision, hearing and/or hand use likely to interfere with assessments
- pregnant or lactating (assessed via pregnancy test)
- unable to follow protocols
- acute suicidality, defined as "Yes" on item 4 of the Columbia Suicide Severity Rating Scale (C-SSRS), (i.e., active suicidal ideation with some intent to act on thoughts), or any endorsement of item 5 (active ideation with specific plan and intent) or any actual, interrupted, aborted attempt or preparatory behavior within the past month.
- symptom threshold considered in the "very severe" range using standard rating scales will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Providence Healthcare System
Providence, Rhode Island, 02908
About this study
Objective: Preliminary studies show that low intensity focused ultrasound (LIFU), a new type of non invasive brain stimulation, may be able to reach deep structures of the brain involved with depression and anxiety, that remain inaccessible using current forms of non-invasive brain stimulation with precision. In this study, the investigators will test if this technique can be used to change brain activity in areas that are connected to depression and anxiety symptoms. The primary objectives of this study are to test the safety and tolerability of LIFU, evaluate the feasibility of using LIFU to reduce brain activity, and evaluate the feasibility of simultaneous fMRI-LIFU. If the results of this study are positive, what the investigators learn will serve as a strong foundation for the future development of innovative treatments for a variety of psychiatric disorders.
Research Procedures: 25 veterans will be recruited. Visits will take place at the VA Providence Healthcare System. During some visits, healthy and patient participants may undergo clinical and research neuroimaging, neuropsychological testing, complete questionnaires, and participate in clinical/neurological assessments. Healthy veterans will not receive LIFU and will only attend 2 study visits. Patients are expected to attend up to 8 visits over 6 weeks. However, some may require up to 6 extended follow-ups after visits 5 or 8, in which case they would attend a total of 11 or 14 visits over 6 months. Two patient visits will include the LIFU application, following FDA safety guidelines. Patients will be assigned either to an experiment in which LIFU stimulation will be delivered immediately prior to a task or to an experiment in which stimulation will be delivered during the task. Within each experiment, patients will be assigned to first receive either LIFU stimulation to the study target or anatomical control. Study staff, but not participants will know which location is being targeted in case safety concerns arise. Safety assessments will be conducted at follow-up visits. A clinician will be available during LIFU administration /follow-up visits. Assuming no injury or other concerns are present, patients will then repeat this process again, receiving stimulation targeting other brain area not previously selected.
- Conditions
- Depression
- Being tested
- Low Intensity Focused Ultrasound
- Keywords
- Functional Neuroimaging, Acoustic Stimulation, Focused Ultrasound
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Intensity Focused UltrasoundDevice
Also called LIFU
Brainsonix BX Pulsar 1002
| Study group | Role | What they receive |
|---|---|---|
| Target Site Low Intensity Focused Ultrasound | Experimental | Low Intensity focused ultrasound of the target region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session. Receives: Device: Low Intensity Focused Ultrasound |
| Control Site Low Intensity Focused Ultrasound | Active comparator | Low Intensity focused ultrasound of the control region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session. Receives: Device: Low Intensity Focused Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of LIFU-related adverse events as assessed by clinical MRI
MRI safety and monitoring will be determined through the review of clinical MRIs. The clinical MRI will be used to detect possible LIFU-induced injury including edema or other injury and microvascular damage. While the investigators believe hyperacute injury to be unlikely, scans at 24 hours and 1-week will be used to monitor for later evolving injury. If injury is detected on any participant at any stage of the study, the investigators will halt all study procedures.
Measured: up to 6 months post LIFU
Incidence of LIFU-related adverse events as assessed by neurological examinations
Neurological exams will be used to detect any possible LIFU-induced neurological changes.
Measured: up to 6 months post LIFU
Incidence of LIFU-related adverse events as assessed by neuropsychological testing
The investigators will evaluate safety using standardized neuropsychological tests at baseline, 24 hours, and 1-week post LIFU. The Repeatable Battery for the Assessment of Neurocognitive Status (RBANS) will be used to measure attention, language, visuospatial/construction, immediate, and delayed memory and to measure any possible LIFU-induced changes across these domains.
Measured: up to 6 months post LIFU
Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication.
Measured: change from baseline to following sonication
BOLD fMRI Signal
BOLD data will be collected before, during, and following LIFU sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
Measured: change from baseline to following sonication
Resting state functional connectivity
Resting state data will be collecting before, during, and following LIFU sonication. Analyses will assess any functional connectivity changes in the brain following sonication.
Measured: change from baseline to following sonication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2021
- Study start28 Sep 2021
- Primary completion4 Mar 2026
- Study completion4 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ocean State Research Institute, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noah S Philip, MD, Principal investigator, VA Providence Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05147142
- Sponsor's protocol ID
- IRB-2020-053
- Acronym
- LIFU
- Status last verified
- Apr 2025
- First submitted
- 9 Nov 2021
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: data may be available via the NIMH Data Archive
Publications
Korb AS, Shellock FG, Cohen MS, Bystritsky A. Low-intensity focused ultrasound pulsation device used during magnetic resonance imaging: evaluation of magnetic resonance imaging-related heating at 3 Tesla/128 MHz. Neuromodulation. 2014 Apr;17(3):236-41; discussion 241. doi: 10.1111/ner.12075. Epub 2013 May 10.
PubMed 23663228Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injury: A First-in-Man Report. Brain Stimul. 2016 Nov-Dec;9(6):940-941. doi: 10.1016/j.brs.2016.07.008. Epub 2016 Jul 22. No abstract available.
PubMed 27567470Pasquinelli C, Hanson LG, Siebner HR, Lee HJ, Thielscher A. Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Brain Stimul. 2019 Nov-Dec;12(6):1367-1380. doi: 10.1016/j.brs.2019.07.024. Epub 2019 Jul 31.
PubMed 31401074Badran BW, Caulfield KA, Stomberg-Firestein S, Summers PM, Dowdle LT, Savoca M, Li X, Austelle CW, Short EB, Borckardt JJ, Spivak N, Bystritsky A, George MS. Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study. Brain Stimul. 2020 Nov-Dec;13(6):1805-1812. doi: 10.1016/j.brs.2020.10.007. Epub 2020 Oct 24.
PubMed 33127579Philip NS, Arulpragasam AR. Reaching for the unreachable: low intensity focused ultrasound for non-invasive deep brain stimulation. Neuropsychopharmacology. 2023 Jan;48(1):251-252. doi: 10.1038/s41386-022-01386-2. No abstract available.
PubMed 35869281Arulpragasam AR, van 't Wout-Frank M, Barredo J, Faucher CR, Greenberg BD, Philip NS. Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Front Psychiatry. 2022 Feb 24;13:825802. doi: 10.3389/fpsyt.2022.825802. eCollection 2022.
PubMed 35280168
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Intensity Focused Ultrasound: a New Paradigm for Depression and Anxiety
- ClinicalTrials.gov ID
- NCT05147142
- Acronym / sponsor ID
- LIFU / IRB-2020-053
- Conditions
- Depression
- Keywords
- Functional Neuroimaging, Acoustic Stimulation, Focused Ultrasound
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Ocean State Research Institute, Inc.University, hospital or other
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 4 Mar 2026 (actual)
- Study completion
- 4 Mar 2026 (actual)
- First posted
- 7 Dec 2021 (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.
Objective: Preliminary studies show that low intensity focused ultrasound (LIFU), a new type of non invasive brain stimulation, may be able to reach deep structures of the brain involved with depression and anxiety, that remain inaccessible using current forms of non-invasive brain stimulation with precision. In this study, the investigators will test if this technique can be used to change brain activity in areas that are connected to depression and anxiety symptoms. The primary objectives of this study are to test the safety and tolerability of LIFU, evaluate the feasibility of using LIFU to reduce brain activity, and evaluate the feasibility of simultaneous fMRI-LIFU. If the results of this study are positive, what the investigators learn will serve as a strong foundation for the future development of innovative treatments for a variety of psychiatric disorders.
Research Procedures: 25 veterans will be recruited. Visits will take place at the VA Providence Healthcare System. During some visits, healthy and patient participants may undergo clinical and research neuroimaging, neuropsychological testing, complete questionnaires, and participate in clinical/neurological assessments. Healthy veterans will not receive LIFU and will only attend 2 study visits. Patients are expected to attend up to 8 visits over 6 weeks. However, some may require up to 6 extended follow-ups after visits 5 or 8, in which case they would attend a total of 11 or 14 visits over 6 months. Two patient visits will include the LIFU application, following FDA safety guidelines. Patients will be assigned either to an experiment in which LIFU stimulation will be delivered immediately prior to a task or to an experiment in which stimulation will be delivered during the task. Within each experiment, patients will be assigned to first receive either LIFU stimulation to the study target or anatomical control. Study staff, but not participants will know which location is being targeted in case safety concerns arise. Safety assessments will be conducted at follow-up visits. A clinician will be available during LIFU administration /follow-up visits. Assuming no injury or other concerns are present, patients will then repeat this process again, receiving stimulation targeting other brain area not previously selected.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Target Site Low Intensity Focused Ultrasound | Experimental | Device: Low Intensity Focused UltrasoundLow Intensity focused ultrasound of the target region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session. |
| Control Site Low Intensity Focused Ultrasound | Active comparator | Device: Low Intensity Focused UltrasoundLow Intensity focused ultrasound of the control region. These are at a fundamental frequency = 650kHz, PRF = 10Hz, pulse width = 5ms, duty cycle = 5%; ISPTA.3 of 720 mW/cm2. As in prior studies, each sonication includes 10 pulsations, each lasting 30s, followed by 30s pause intervals; two 10-minute administrations provided per LIFU session. |
Who may qualify
- Ages
- 22 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients must meet DSM-5 criteria for major depressive disorder with and without anxiety symptoms
- Patients must also be symptomatic (i.e. symptom severity above clinical thresholds using standard rating scales) and, if relevant, stable treatment(s) for >6 weeks.
Key exclusion criteria (12 listed)
- history of seizure disorder or serious neurologic illness including dementia
- structural or neurologic abnormalities present or in close proximity to sonication site for patients (e.g., clinically significant calcification as might be observed in Fahr disease)
- history of brain surgery, iv) pacemaker or implanted central nervous system device
- greater than mild traumatic brain injury, or any head injury within sixty days of participation
- greater than moderate alcohol or substance use disorders (last six months; excluding nicotine/caffeine)
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 |
|---|---|---|
| Low Intensity Focused UltrasoundAlso: LIFUBrainsonix BX Pulsar 1002 | Device | Control Site Low Intensity Focused Ultrasound, Target Site Low Intensity Focused Ultrasound |
Primary outcome
Incidence of LIFU-related adverse events as assessed by clinical MRI
Time frame: up to 6 months post LIFU
MRI safety and monitoring will be determined through the review of clinical MRIs. The clinical MRI will be used to detect possible LIFU-induced injury including edema or other injury and microvascular damage. While the investigators believe hyperacute injury to be unlikely, scans at 24 hours and 1-week will be used to monitor for later evolving injury. If injury is detected on any participant at any stage of the study, the investigators will halt all study procedures.
Incidence of LIFU-related adverse events as assessed by neurological examinations
Time frame: up to 6 months post LIFU
Neurological exams will be used to detect any possible LIFU-induced neurological changes.
Incidence of LIFU-related adverse events as assessed by neuropsychological testing
Time frame: up to 6 months post LIFU
The investigators will evaluate safety using standardized neuropsychological tests at baseline, 24 hours, and 1-week post LIFU. The Repeatable Battery for the Assessment of Neurocognitive Status (RBANS) will be used to measure attention, language, visuospatial/construction, immediate, and delayed memory and to measure any possible LIFU-induced changes across these domains.
Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
Time frame: change from baseline to following sonication
Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication.
BOLD fMRI Signal
Time frame: change from baseline to following sonication
BOLD data will be collected before, during, and following LIFU sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
Resting state functional connectivity
Time frame: change from baseline to following sonication
Resting state data will be collecting before, during, and following LIFU sonication. Analyses will assess any functional connectivity changes in the brain following sonication.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Background: PubMed 23663228Korb AS, Shellock FG, Cohen MS, Bystritsky A. Low-intensity focused ultrasound pulsation device used during magnetic resonance imaging: evaluation of magnetic resonance imaging-related heating at 3 Tesla/128 MHz. Neuromodulation. 2014 Apr;17(3):236-41; discussion 241. doi: 10.1111/ner.12075. Epub 2013 May 10.
- Background: PubMed 27567470Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injury: A First-in-Man Report. Brain Stimul. 2016 Nov-Dec;9(6):940-941. doi: 10.1016/j.brs.2016.07.008. Epub 2016 Jul 22. No abstract available.
- Background: PubMed 31401074Pasquinelli C, Hanson LG, Siebner HR, Lee HJ, Thielscher A. Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Brain Stimul. 2019 Nov-Dec;12(6):1367-1380. doi: 10.1016/j.brs.2019.07.024. Epub 2019 Jul 31.
- Background: PubMed 33127579Badran BW, Caulfield KA, Stomberg-Firestein S, Summers PM, Dowdle LT, Savoca M, Li X, Austelle CW, Short EB, Borckardt JJ, Spivak N, Bystritsky A, George MS. Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study. Brain Stimul. 2020 Nov-Dec;13(6):1805-1812. doi: 10.1016/j.brs.2020.10.007. Epub 2020 Oct 24.
- Background: PubMed 35869281Philip NS, Arulpragasam AR. Reaching for the unreachable: low intensity focused ultrasound for non-invasive deep brain stimulation. Neuropsychopharmacology. 2023 Jan;48(1):251-252. doi: 10.1038/s41386-022-01386-2. No abstract available.
- Background: PubMed 35280168Arulpragasam AR, van 't Wout-Frank M, Barredo J, Faucher CR, Greenberg BD, Philip NS. Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Front Psychiatry. 2022 Feb 24;13:825802. doi: 10.3389/fpsyt.2022.825802. eCollection 2022.
- Individual participant dataSharing planned: No. data may be available via the NIMH Data Archive
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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.
Noah S Philip, MD principal investigator
VA Providence Healthcare System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low Intensity Focused Ultrasound in people with Depression, run by Ocean State Research Institute, Inc. 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 2 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: finished, as of the sponsor's last update on 24 Jul 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of LIFU-related adverse events as assessed by clinical MRI (time frame: up to 6 months post LIFU). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05147142, which also lists 6 linked publications.
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 24 Jul 2026.