NCT07508696

Brief Summary

Experiment 1: Modulation of Physiological Tremor in Healthy Volunteers Thirty healthy volunteers will undergo TUS targeting the dentate nucleus in a randomized, double-blinded crossover design. Tremor amplitude, induced by a 15 g weight, will be measured using an accelerometer, and EEG will assess neural oscillations and cerebello-thalamo-cortical connectivity. Stimulation will include short-term (1 minute on/off for 12 minutes) and long-term (30 minutes) protocols, as well as closed-loop TUS for phase-specific effects. This experiment aims to optimize stimulation parameters and explore the dentate nucleus's role in tremor generation. Experiment 2: Tremor Modulation in Essential Tremor Patients Thirty ET patients will receive TUS targeting the dentate nucleus with optimized parameters from Experiment 1 in a randomized crossover design. The best protocol from previous experiment will be tested here. Tremor amplitude and EEG will be recorded to assess short- and long-term effects of TUS on pathological tremor.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
28mo left

Started Jun 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 19, 2026

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 2, 2026

Completed
2 months until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2028

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

April 2, 2026

Status Verified

March 1, 2026

Enrollment Period

2 years

First QC Date

March 19, 2026

Last Update Submit

March 31, 2026

Conditions

Essential Tremor

Keywords

transcranial focused ultrasound stimulationTUSEssential TremorETMovement disordersNeuromodulationNIBSnon-invasive brain stimulation

Outcome Measures

Primary Outcomes (2)

  • Tremor amplitude

    Extracted from accelerometer data. The PCA component will be calculated by combining data from all three accelerometer axis (x, y and z). The power spectral density average of this PCA component will be calculated before (1min), during and after (1 min) stimulation. The primary outcome is the change in tremor amplitude (m/s²) across pre-, during-, and post-TUS conditions.

    Experiment 1 (short-term effects): 1-minute recording segments up to 10 minutes after stimulation, Experiment 1(long-term effects): Up to 30 minutes after stimulation Experiment 2 (Essential tremor): Up to 30 minutes after stimulation

  • Tremor frequency

    Tremor frequency will be derived from the same one-dimensional signal obtained via principal component analysis (PCA) of the triaxial accelerometer data. The power spectral density (PSD) will be estimated using Welch's method for each recording segment (pre-TUS, during TUS, post-TUS). The dominant tremor frequency will be defined as the frequency corresponding to the maximum PSD value within the predefined tremor band (e.g., 4-12 Hz) (expressed in Hz)

    Experiment 1 (short-term effects): 1-minute recording segments up to 10 minutes after stimulation, Experiment 1 (long-term effects): Up to 30 minutes after stimulation Experiment 2 (Essential tremor): Up to 30 minutes after stimulation

Secondary Outcomes (3)

  • EEG oscillatory activity

    Experiment 1 (short-term effects): 1-minute segments of on/off stimulation from 10 minutes before stimulation up until 10 minutes after stimulation Experiment 1 (long-term effects) & 2: 10 minutes before stimulation up until 30 minutes after stimulation

  • EEG Phase

    Experiment 1 (short-term): During 1-minute segments of ON-stimulation Experiment 1 (long-term): During full 30-minute stimulation session. Experiment 2 (essential tremor): During full 30-minute stimulation session.

  • Phase-Locking Value

    Experiment 1 (short-term): During 1-minute segments of ON-stimulation Experiment 1 (long-term): During full 30-minute stimulation session. Experiment 2 (essential tremor): During full 30-minute stimulation session.

Study Arms (2)

On-target to sham

EXPERIMENTAL

Participants in this arm will receive on-target stimulation first, followed by the sham condition

Device: Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by BrainboxDevice: Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox

Sham to on-target

EXPERIMENTAL

Participants in this arm will receive sham stimulation first, followed by the on-target stimulation

Device: Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by BrainboxDevice: Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox

Interventions

Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by BrainboxDEVICE

This study will look at both physiological tremor in healthy volunteers and pathological tremor in ET patients. A set of parameters will be tested in healthy volunteers and the optimal combination of pulse repetition frequency (PRF) and pulse duration (PD) will be selected. A closed-loop system will also be tested where the timing of the ultrasound pulses is locked to the peak or the trough of the measured tremor and can adjust in real-time.

On-target to shamSham to on-target
Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by BrainboxDEVICE

This condition will serve as the active control (sham stimulation).

On-target to shamSham to on-target

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Experiment 1: Healthy Volunteers
  • Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
  • Participants aged 18-55 years
  • Male of female
  • Good health with no history of serious mental illness or implanted metal
  • Willingness to adhere to the TUS and MRI study schedule
  • Willingness to avoid caffeine and alcohol intake for at least 2 h prior to the investigation
  • Experiment 2: ET Patients
  • Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
  • Participants aged 18-75 years
  • Male of female
  • Diagnosis of ET as confirmed from clinical history and examination by a movement disorder neurologist
  • Willingness to adhere to the TUS and MRI study schedule
  • Willingness to avoid caffeine and alcohol intake for at least 2 h prior to the investigation

You may not qualify if:

  • Experiment 1: Healthy volunteers
  • Currently taking any psychotropic medication
  • Any head trauma resulting in loss of consciousness
  • Diagnosed with a serious mental illness
  • Alcohol or substance abuse or dependence (other than tobacco) in the past week
  • Currently in treatment for a psychiatric condition
  • Pregnancy (a test will be scheduled by the research team)
  • Personal or family history of seizures or epilepsy
  • Claustrophobia or inability to stay still in the MR scanner environment
  • Any metal in the body that is not MRI-compatible
  • Serious history of migraines
  • Hair in dreadlocks, braids, or weave (not possible to position ultrasound transducer)
  • orthopedic forearm or hand problems
  • Inability to adhere to the experimental schedule.
  • Experiment 2: ET Patients
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

BrainsHub

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Essential TremorMovement Disorders

Condition Hierarchy (Ancestors)

Central Nervous System DiseasesNervous System Diseases

Central Study Contacts

Robrecht W. Pieters, Master

CONTACT

+32 470 19 39 83robrecht.pieters@kuleuven.be

Myles Mc Laughlin, Professor

CONTACT

+32 468 24 91 64myles.mclaughlin@kuleuven.be

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Both the participant and the investigator applying the TUS will be blinded to the stimulation condition (on-target or active control).
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: Each participant will undergo two conditions: on-target transcranial focused ultrasound stimulation (TUS) to the dentate nucleus and off-target (sham) stimulation.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

March 19, 2026

First Posted

April 2, 2026

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

October 1, 2028

Last Updated

April 2, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

BE(1)