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

NCT ID: NCT05147142

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-28

Study Completion Date

2026-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Depression

Keywords

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Functional Neuroimaging Acoustic Stimulation Focused Ultrasound

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants
Single blind administration

Study Groups

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Target Site Low Intensity Focused Ultrasound

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.

Group Type EXPERIMENTAL

Low Intensity Focused Ultrasound

Intervention Type DEVICE

Brainsonix BX Pulsar 1002

Control Site Low Intensity Focused Ultrasound

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.

Group Type ACTIVE_COMPARATOR

Low Intensity Focused Ultrasound

Intervention Type DEVICE

Brainsonix BX Pulsar 1002

Interventions

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Low Intensity Focused Ultrasound

Brainsonix BX Pulsar 1002

Intervention Type DEVICE

Other Intervention Names

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LIFU

Eligibility Criteria

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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.
Minimum Eligible Age

22 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ocean State Research Institute, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Noah S Philip, MD

Role: PRINCIPAL_INVESTIGATOR

VA Providence Healthcare System

Locations

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VA Providence Healthcare System

Providence, Rhode Island, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Noah S Philip, MD

Role: CONTACT

Phone: 4012737100

Email: [email protected]

Emily Aiken, MA

Role: CONTACT

Phone: 4012737100

Email: [email protected]

Facility Contacts

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Alison Gorbatov, JD

Role: primary

Amanda R Arulpragasam, PhD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 23663228 (View on PubMed)

Monti 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.

Reference Type BACKGROUND
PMID: 27567470 (View on PubMed)

Pasquinelli 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.

Reference Type BACKGROUND
PMID: 31401074 (View on PubMed)

Badran 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.

Reference Type BACKGROUND
PMID: 33127579 (View on PubMed)

Philip 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.

Reference Type BACKGROUND
PMID: 35869281 (View on PubMed)

Arulpragasam 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.

Reference Type BACKGROUND
PMID: 35280168 (View on PubMed)

Other Identifiers

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IRB-2020-053

Identifier Type: -

Identifier Source: org_study_id