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OpenTrials
Completed

NCT Number: NCT05147142

Low Intensity Focused Ultrasound: a New Paradigm for Depression and Anxiety

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.

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Key information

Conditions

Depression Behavior Behavioral Symptoms

Age range

22 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

VA Providence Healthcare System

Providence, Rhode Island, 02908, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

US military Veterans

Inclusion criteria

  • 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.

Exclusion criteria

  • 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)
  • 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.

Treatment and study plan

Low Intensity Focused Ultrasound

Device

Brainsonix BX Pulsar 1002

Other names: LIFU

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Sponsors and collaborators

Lead sponsor

Ocean State Research Institute, Inc.

Other

Registry information

Acronym: LIFU

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Dec 7, 2021
Registry last updated
Jul 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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