Ultrasound Neuromodulation in Essential Tremor

NCT06610877 | Recruiting FDA Device

• 1 other identifier: P0573974
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to test whether low-intensity focused ultrasound (LIFU) (low energy sound waves) cause temporary changes in brain activity and behavior when directed at particular parts of the brain. By targeting LIFU to the parts of the brain thought to be responsible for essential tremor (ET), and measuring any associated improvement in tremor, the investigators hope to show that LIFU can be a useful tool for studying the brain circuits responsible for tremor and other brain disorders.

Conditions

Neuromodulation; Essential Tremor

Keywords

Essential Tremor; Neuromodulation; Focused Ultrasound; brain functional connectivity

Outcome Measures

Primary Outcomes (1)

• Reduction in tremor

  The investigators will screen ultrasound parameters through repeated sonications within the same session (up to 25, depending on patient response) to determine which parameter set is most effective at reducing tremor in each participant as measured by wrist accelerometers (reduction in tremor power from baseline in the characteristic ET range of 4-12 Hz). Stimulation protocols will consist of 5 seconds of active stimulation followed by 10 seconds of no stimulation repeated four times (total 60 s). After each 60-s stimulation, there will be a delay of 3 minutes, during which the investigators will monitor tremor severity every 60 seconds through quantitative accelerometer recordings. If a change in tremor severity greater than 50% is found in the post-LIFU period compared to the pre-LIFU baseline, the investigators will wait until tremor returns to a level comparable to baseline before proceeding with additional stimulations.

  For 3 minutes immediately after the application of each sonication protocol

Secondary Outcomes (1)

• Increases or decreases in functional connectivity of brain networks

  20-30 minute MRI scan at the end of the 3-4 hour experimental session

Study Arms (2)

To determine the most effective stimulation parameters for DRTT LIFU neuromodulation.

EXPERIMENTAL

Investigators will record wrist accelerometer signals while participants maintain standardized postures that maximally elicit their tremor before, during, and after delivering LIFU stimulation.

Device: Focused Ultrasound Neuromodulation - Sham Control; Device: Focused ultrasound neuromodulation

Defocusing lens

SHAM COMPARATOR

This arm will be exactly the same as that of the active arm with the exception that a defocusing lens will be fitted to the ultrasound device which will cause the ultrasound energy to be dispersed rather than directed at the target structure.

Device: Focused Ultrasound Neuromodulation - Sham Control

Interventions

Focused Ultrasound Neuromodulation - Sham Control DEVICE

Each ultrasound stimulation protocol will last for 60 seconds, consisting of 4 pulse trains of 5 seconds duration separated by 10 second intervals without stimulation. Across successive stimulation protocols (up to 25/patient) investigators will systematically vary pulse repetition frequency, duty cycle, and acoustic intensity to determine how these parameters contribute to the behavioral effect (transient tremor reduction). Parameters will be shuffled to control for group-level carry over effects. A defocusing lens will be in place during the session to test the difference between focused and unfoucused ultrasound while controlling for non-specific auditory and somatosensory confounds.

Defocusing lens; To determine the most effective stimulation parameters for DRTT LIFU neuromodulation.

Focused ultrasound neuromodulation DEVICE

Each ultrasound stimulation protocol will last for 60 seconds, consisting of 4 pulse trains of 5 seconds duration separated by 10 second intervals without stimulation. Across successive stimulation protocols (up to 25/patient) investigators will systematically vary pulse repetition frequency, duty cycle, and acoustic intensity to determine how these parameters contribute to the behavioral effect (transient tremor reduction) in each patient. Parameters will be shuffled to control for group-level carry over effects and will include sham (unfocused or off-target stimulation) conditions to control for non-specific auditory confounds.

To determine the most effective stimulation parameters for DRTT LIFU neuromodulation.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with medically refractory tremor scheduled to undergo MR-guided high-intensity focused ultrasound (HIFU) thalamotomy to treat their tremor at UCSF.

You may not qualify if:

• Due to the logistical complexity of performing MRI in patients with MR-conditional pacemakers (need for device and patient monitoring), patients with pacemakers will be excluded from enrollment. All other patients undergoing HIFU thalamotomy for tremor will be eligible for enrollment.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Focused Ultrasound Foundation: collaborator

Study Sites (1)

Pritzker Building, UCSF

San Francisco, California, 94107, United States

RECRUITING

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Leo Sugrue, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leo P. Sugrue, MD, PhD

CONTACT

415-353-9056; leo.sugrue@ucsf.edu

Tommaso Di Ianni, PhD

CONTACT

tommaso.diianni@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be unaware of which focused ultrasound protocols are being applied when or whether the applied protocol is considered to be a candidate active stimulation or sham protocol.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a within-subject repeated-measures interventional study to test which of a set of LIFU stimulation parameters are most effective at producing temporary tremor reduction when applied to the DRTT - the white matter circuit involved in essential tremor. During a single session up to 25 different stimulation protocols will be tested in each participant in a shuffled manner including sham stimulation protocols.

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 24, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)