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

March 8, 2023 updated by: Ocean State Research Institute, Inc.

Objective: Preliminary studies show that low intensity focused ultrasound (LIFU), a new type of non invasive brain stimulation (NIBS), may be able to reach deep structures of the brain involved with depression and anxiety, that remain inaccessible using current forms of NIBS 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 patient and 25 healthy 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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02908
        • Recruiting
        • VA Providence Healthcare System
        • Contact:
        • Contact:
        • Principal Investigator:
          • Noah S Philip, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.
  • Healthy volunteers must have an absence of psychiatric disorders ( >6 months; lifetime for major depression and PTSD) and absence of psychiatric medications of therapy for >6 months

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: Low Intensity Focused Ultrasound
Brainsonix BX Pulsar 1002
Other Names:
  • LIFU
Active Comparator: 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.
Device: Low Intensity Focused Ultrasound
Brainsonix BX Pulsar 1002
Other Names:
  • LIFU
No Intervention: Healthy Control
25 age- and sex-matched healthy controls will be recruited and complete fMRI tasks. They will not receive low intensity focused ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
up to 6 months post LIFU
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.
up to 6 months post LIFU
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.
up to 6 months post LIFU
BOLD fMRI Signal
Time Frame: change from baseline immediately following sonication, at 24 hours, and 1 week
BOLD data will be collected before, during, and following LIFU sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
change from baseline immediately following sonication, at 24 hours, and 1 week
Resting state functional connectivity
Time Frame: change from baseline immediately following sonication, at 24 hours, and 1 week
Resting state data will be collecting before, during, and following LIFU sonication. Analyses will assess any functional connectivity changes in the brain following sonication.
change from baseline immediately following sonication, at 24 hours, and 1 week
Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
Time Frame: change from baseline immediately following sonication, at 24 hours, and 1 week
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.
change from baseline immediately following sonication, at 24 hours, and 1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ocean State Research Institute, Inc.

Investigators

  • Principal Investigator: Noah S Philip, MD, VA Providence Healthcare System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2021

Primary Completion (Anticipated)

July 30, 2025

Study Completion (Anticipated)

September 30, 2025

Study Registration Dates

First Submitted

November 9, 2021

First Submitted That Met QC Criteria

November 23, 2021

First Posted (Actual)

December 7, 2021

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

March 8, 2023

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-2020-053

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data may be available via the NIMH Data Archive

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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