Dose-Dependent Effects of Low-Intensity Focused Ultrasound

NCT07099950 | Recruiting DMC

• 1 other identifier: 2024-010
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Low-intensity focused ultrasound (LIFU) has emerged as a tool to modulate the activity of deep brain structures noninvasively and reversibly, with anatomical precision. Following the results of a pilot study in which the investigators observed target engagement when LIFU was applied to the anterior limb of the internal capsule, the investigators now propose to determine the dose-response relationships of LIFU when applied to deep white matter tracts of the human brain. The investigators hope a successful study will be rapidly translatable into clinical trials seeking to understand mechanistic brain circuit-symptom relationships in major psychiatric disorders.

Conditions

Healthy Controls

Keywords

Low-Intensity Focused Ultrasound; Functional Connectivity

Outcome Measures

Primary Outcomes (1)

• Post-Sonication Changes in Tissue Engagement

  Changes in resting-state functional (fMRI) connectivity (FC) between thalamus and both subgenual (sgCC) and orbitofrontal (OFC) cortices after one vs. after three-epoch LIFU.

  Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.

Secondary Outcomes (1)

• Post-Sonication Changes in Functional Connectivity with Respect to Structural Connectivity

  Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.

Study Arms (2)

Single Dose (1-epoch)

EXPERIMENTAL

An 80-second train of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts). It is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 estimated derated ISPPA). Any modeling of actual energy delivery will be made a posteriori employing BabelBrain® software embedded in the Brainsight® neuronavigation system.

Other: Low-intensity focused ultrasound

Multiple Doses (3-epoch)

EXPERIMENTAL

Three 80-second trains of 20-millisecond bursts of ultrasound (0.5 MHz), repeated every 200 milliseconds (400 bursts) will be administered, separated by 30 seconds each. Again, it is estimated a 75% tissue attenuation of energy when the ultrasound wave reaches its target, therefore the investigators will set the free-field Intensity Spatial-Peak Pulse-Average (ISPPA) at 9.04 Watt /cm2 or 518 kPascal (to achieve 2.26 Watt/cm2 derated ISPPA). See above for a posteriori acoustic energy modeling.

Other: Low-intensity focused ultrasound

Interventions

Low-intensity focused ultrasound OTHER

80-second stimulus with an estimated tissue ISSPA=2.26 W/cm2, administered as a single dose (1-epoch), or in multiple doses (3-epoch).

Multiple Doses (3-epoch); Single Dose (1-epoch)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years.
• Body mass index 17-38 kg/m2.
• Fluent English speaker, capable of providing written informed consent.
• Overall Anxiety Severity and Impairment Scale \<8 and Patient Health Questionnaire-9 \<10
• A person of childbearing potential must have a negative urine pregnancy test at screening
• Consent that random observations of pathology are possible (e.g., brain abnormality seen during imaging).

You may not qualify if:

• Inability to provide informed consent including medical, psychiatric, or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or complete the study.
• No telephone or easy access to telephone
• Has active suicidal ideation (as measured by Suicide-Risk-Assessment-C-SSRS "Yes" answers to items 3, 4, or 5 Suicidal Ideation-Past 1 month section, or any "Yes" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months
• Has positive test result(s) for alcohol of abuse (including methadone, opiates, cocaine, amphetamine/methamphetamine and ecstasy), or substance use disorder including alcohol, stimulants, sedatives, and cannabis exceeding mild severity in the last 6 months
• Has a lifetime APA Diagnostic and Statistical Manual of Mental Disorders (DSM)-5th edition including major depression, generalized anxiety disorder, specific phobias, panic disorder, post-traumatic stress disorder, schizophrenia spectrum and other psychotic disorders, obsessive-compulsive disorder, or bipolar disorder.
• Benzodiazepines or anticonvulsants in the 7 days prior to participation.
• MRI contradictions as detected by the MRI Safety Screen including claustrophobia and unwillingness and inability to complete scans (e.g., unable to lie on one's back for 60 mins.
• Clinical history of relevant structural pathology of the central nervous system, including Parkinson's disease, multiple sclerosis, and brain malignant neoplasia.
• History of unstable liver or renal insufficiency; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, hematological, rheumatological, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit or confound the protocol-specified assessments, including uncontrolled diabetes mellitus (ss evidenced by fasting glycemia ≥ 120 mg/dL or hemoglobin A1c ≥ 6.5%) or hypertension (as evidenced by two consecutive readings ≥ 140/90 mmHg) to ensure medical stability throughout this longitudinal study.
• Moderate-to-severe traumatic brain injury or any other clinical neurocognitive disorder.
• Clinical history of at least minor neurocognitive disorder of any origin.
• Prescription of a medication outside of the accepted range, as determined by best clinical practices and current research.
• Use of any psychotropic medication.
• Unwillingness or inability to complete any major aspects of the study protocol.
• Prior neurosurgery.

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

RECRUITING

Central Study Contacts

Salvador M Guinjoan, MD, PhD

CONTACT

918-502-5119; sguinjoan@laureateinstitute.org

Danielle E Clark, MA

CONTACT

918-701-9610; dclark@laureateinstitute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The stimulation administration programmer will be unblinded to the type of intervention (1-epoch vs 3-epoch). Participant, study staff, and principal investigator will be blinded to the intervention.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An exploratory hypothesis is that stimulation of anteromedial structures of the telencephalic cortex of the right hemisphere and their connections with subcortical structures will lead to detectable changes in functional connectivity between these structures in a dose-dependent manner. In this study, the investigators will use a double-blind, randomized cross-over design employing either 1-LIFU or 3-LIFU. The proposed design parsimoniously follows the approved pilot study.

Study Record Dates

• First Submitted: June 12, 2025
• First Posted: August 1, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)