Healthy ControlsNCT07099950
Dose-Dependent Effects of Low-Intensity Focused Ultrasound
A study testing Low-intensity focused ultrasound in people with Healthy Controls, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Controls
- What is being tested?
- Low-intensity focused ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2025to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- Non-correctable vision or hearing.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74136
Salvador M Guinjoan, MD, PhD, 918-502-5119, sguinjoan@laureateinstitute.org
Danielle E Clark, MA, 918-701-9610, dclark@laureateinstitute.org
About this study
Official title: Dose-Dependent Functional Connectivity Effects of Low-Intensity Focused Ultrasound Applied to Deep White Matter Tracts in Humans
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.
Read the detailed description
Low intensity focused ultrasound (LIFU) is a novel technique producing noninvasive, reversible, and anatomically precise neuromodulation of deep structures in the brain. Thus far, it has been successfully employed in humans to modulate the activity of gray matter hubs, including amygdala, thalamus, and cerebral cortex. Burgeoning in vitro data shows that LIFU is also a powerful modulator of axonal conduction, by operating mechanosensitive TRAAK potassium channels in nodes of Ranvier. In a recently completed pilot study (NCT 05697172; FDA non-significant risk), the investigators translated those findings to human subjects by applying LIFU to deep brain white matter tracts, reasoning that a successful study would allow the modulation of large-scale brain circuits and thus potentially explore their mechanistic relationship with normal and abnormal behavior. Specifically, the investigators observed that a single sonication applied to tracts traversing the anterior limb of the internal capsule (ALIC) produces a functional disconnection of the connected gray matter regions, as assessed with resting state functional magnetic resonance imaging (fMRI). Now the investigators propose to define the dose-dependent effects of LIFU applied to white matter tracts regarding both intensity and duration of its neuromodulatory effects. The investigators plan to study 60 healthy adults who will be randomly exposed to two different doses of LIFU applied to tracts connecting the thalamus with the subgenual cingulate (SGCC) and orbitofrontal (OFC) cortices, namely one and three LIFU epochs (as employed in our pilot study: 80 s duration; 2.26 Watt/cm2 derated tissue peak pulse average intensity; 10% duty cycle, 500 kHz). The target white matter tracts will be defined in each individual participant by means of probabilistic tractography. The Aim 1 of this proposal is to determine the relationship between LIFU dose and intensity of target engagement in terms of decreased fMRI functional connectivity between the gray matter regions connected by the sonicated white matter tracts (i.e., thalamus and both SGCC and OFC). Aim 2 is to determine the influence of baseline structural (number of connecting streamlines) and functional (fMRI connectivity) on the dose-dependent LIFU modulation effects. In Aim 3 the investigators will determine the duration of the neuromodulation effect of the two different doses of LIFU. A successful study will result in the definition of dose-response relationships between white matter LIFU modulation and engagement of the targeted brain circuit. This will pave the way for the development of mechanistic studies consistently linking aberrant function of large-scale brain circuits and basic behavioral processes, with the long-term goal of improving the definition of precision neuromodulation targets in treatment-resistant depression and other psychiatric disorders.
- Conditions
- Healthy Controls
- Being tested
- Low-intensity focused ultrasound
- Keywords
- Low-Intensity Focused Ultrasound, Functional Connectivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-intensity focused ultrasoundOther
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Low-intensity focused ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Establishment of a Pearson correlation between the number of thalamo-OFC and thalamo-sgCC streamlines, and resting-state fMRI FC changes between the thalamus and OFC or sgCC regions, respectively, after one- and three-LIFU epoch stimulation.
Measured: Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start22 Apr 2025
- Primary completionAug 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ControlsStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07099950
- Sponsor's protocol ID
- 2024-010
- Status last verified
- Oct 2025
- First submitted
- 12 Jun 2025
- Last updated
- 16 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Dependent Functional Connectivity Effects of Low-Intensity Focused Ultrasound Applied to Deep White Matter Tracts in Humans
- ClinicalTrials.gov ID
- NCT07099950
- Acronym / sponsor ID
- 2024-010
- Conditions
- Healthy Controls
- Keywords
- Low-Intensity Focused Ultrasound, Functional Connectivity
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Study start
- 22 Apr 2025 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 1 Aug 2025 (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.
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.
Detailed description
Low intensity focused ultrasound (LIFU) is a novel technique producing noninvasive, reversible, and anatomically precise neuromodulation of deep structures in the brain. Thus far, it has been successfully employed in humans to modulate the activity of gray matter hubs, including amygdala, thalamus, and cerebral cortex. Burgeoning in vitro data shows that LIFU is also a powerful modulator of axonal conduction, by operating mechanosensitive TRAAK potassium channels in nodes of Ranvier. In a recently completed pilot study (NCT 05697172; FDA non-significant risk), the investigators translated those findings to human subjects by applying LIFU to deep brain white matter tracts, reasoning that a successful study would allow the modulation of large-scale brain circuits and thus potentially explore their mechanistic relationship with normal and abnormal behavior. Specifically, the investigators observed that a single sonication applied to tracts traversing the anterior limb of the internal capsule (ALIC) produces a functional disconnection of the connected gray matter regions, as assessed with resting state functional magnetic resonance imaging (fMRI). Now the investigators propose to define the dose-dependent effects of LIFU applied to white matter tracts regarding both intensity and duration of its neuromodulatory effects. The investigators plan to study 60 healthy adults who will be randomly exposed to two different doses of LIFU applied to tracts connecting the thalamus with the subgenual cingulate (SGCC) and orbitofrontal (OFC) cortices, namely one and three LIFU epochs (as employed in our pilot study: 80 s duration; 2.26 Watt/cm2 derated tissue peak pulse average intensity; 10% duty cycle, 500 kHz). The target white matter tracts will be defined in each individual participant by means of probabilistic tractography. The Aim 1 of this proposal is to determine the relationship between LIFU dose and intensity of target engagement in terms of decreased fMRI functional connectivity between the gray matter regions connected by the sonicated white matter tracts (i.e., thalamus and both SGCC and OFC). Aim 2 is to determine the influence of baseline structural (number of connecting streamlines) and functional (fMRI connectivity) on the dose-dependent LIFU modulation effects. In Aim 3 the investigators will determine the duration of the neuromodulation effect of the two different doses of LIFU. A successful study will result in the definition of dose-response relationships between white matter LIFU modulation and engagement of the targeted brain circuit. This will pave the way for the development of mechanistic studies consistently linking aberrant function of large-scale brain circuits and basic behavioral processes, with the long-term goal of improving the definition of precision neuromodulation targets in treatment-resistant depression and other psychiatric disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Single Dose (1-epoch) | Experimental | Other: Low-intensity focused ultrasoundAn 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. |
| Multiple Doses (3-epoch) | Experimental | Other: Low-intensity focused ultrasoundThree 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
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 ultrasound80-second stimulus with an estimated tissue ISSPA=2.26 W/cm2, administered as a single dose (1-epoch), or in multiple doses (3-epoch). | Other | Multiple Doses (3-epoch), Single Dose (1-epoch) |
Primary outcome
Post-Sonication Changes in Tissue Engagement
Time frame: Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.
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.
1 secondary outcome
Post-Sonication Changes in Functional Connectivity with Respect to Structural Connectivity
Time frame: Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Individual participant dataSharing planned: No
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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.
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 Healthy Controls, run by Laureate Institute for Brain Research, 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 6 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 16 Oct 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Salvador M Guinjoan, MD, PhD (918-502-5119, sguinjoan@laureateinstitute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-Sonication Changes in Tissue Engagement (time frame: Pre- vs up to 30 minutes post-sonication for 1-epoch vs 3-epoch LIFU.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2025.