Essential Tremor
Conditions
Brief summary
The purpose of this research is to learn more about how the brain works in people with essential tremor, and how it changes after treatment with High-Intensity Focused Ultrasound (HiFU). Essential tremor is a movement disorder that causes shaking, usually in the hands, and can make everyday tasks difficult. HiFU is a treatment that uses focused sound waves to target a small area in the brain involved in tremor. In this study, the investigators aim to understand how this treatment affects the brain's networks by using safe, non-invasive tests such as brain imaging, brain wave recordings, and movement assessments.
Detailed description
Participation in this study will last for approximately eight months. Participants will be asked to attend a total of six study visits. These include a screening visit to see if a potential participant qualifies for the study, an assessment visit before treatment and treatment visits. Prior to and after treatment (one day, six weeks, and six months after treatment), participants will have Magnetoencephalography (MEG), Functional Magnetic Resonance Imaging (fMRI), Sensor-Based Gait and Motor Function Assessments and Self-Report Questionnaires.
Interventions
DIAGNOSTIC_TESTMRI and fMRI scans
functional MRI, diffusion tensor imaging, anatomical MRI
DIAGNOSTIC_TESTMEG
non-invasive electrophysiological technology that provides high temporal and spatial resolution to examine large-scale cortical dynamics.
DIAGNOSTIC_TESTSensor-based motor assessments
research-grade wearable sensors equipped with gyroscopes and accelerometers to precisely and accurately quantify patients' tremors. These sensors will be worn on the wrist or finger, capturing data as patients perform standardized tremor assessment tasks, such as spiral drawing task, writing task, commonly used in essential tremor evaluation. Gait and balance assessments will be conducted by synchronizing multiple sensors placed on the upper and lower extremities as well as the midline. Gait and balance data will be collected during tasks such as the 7-meter walk test, 360-degree turn test, and postural sway.
OTHERClinical evaluations
vital signs, health status review, and neurological exam.
OTHERQuestionnaires and rating scales that
daily functioning, mood, memory, and tremor
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Age \>50 years and \<85 years * Refractory to at least 2 first line tremor medications * Skull Density Ratio (SDR) \> = 0.35 Exclusion: * MR/MEG incompatible implants and implantable devices (ex: pacemaker) * Head tremor interfering with MEG recording * Severe depression and/or anxiety * Severe cognitive impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in brain electrical activity measured by magnetoencephalography (MEG) before and after treatment with focused ultrasound | baseline to 7 months | Brain electrical activity will be recorded using magnetoencephalography (MEG) before treatment and at follow-up visits after treatment. MEG signals are collected as time-series data and processed to derive quantitative measures of functional brain connectivity that inform how interconnected different brain regions are. The primary outcome is the average change in these connectivity measures from pre-treatment baseline to post-treatment follow-up across participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between change in tremor amplitude and change in MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the correlation between the change in wearable sensor-derived tremor amplitude (acceleration magnitude, m/s2) and the change in MEG connectivity metrics. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change in tremor frequency and change in MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the correlation between the change in wearable sensor-derived tremor frequency (Hz) and the change in MEG connectivity metrics. Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change in gait parameters and change in MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the correlation between the change in wearable sensor-derived gait parameters during a standardized walk test and the change in MEG connectivity metrics. Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change in postural sway and change in MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the correlation between the change in wearable balance sensor-derived postural sway and the change in MEG connectivity metrics. Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change in 360-degree turn performance and change in MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the correlation between the change in 360-degree turn performance (duration and number of steps), obtained from wearable sensors, and the change in MEG connectivity metrics. Correlation coefficient (r) ranging from -1 to 1 |
| Change from Baseline in MEG-derived Functional Connectivity Strength | Baseline (pre-treatment) to 6 months post-treatment | Assessment of the longitudinal change in MEG-derived functional connectivity strength over multiple time points. Unitless connectivity coefficient, reported as Z-score difference |
| Change from Baseline in MEG-derived Directed Connectivity | Baseline (pre-treatment) to 6 months post-treatment | Assessment of the longitudinal change in MEG-derived directed (effective) connectivity over multiple time points. Unitless influence coefficient, reported as Z-score difference |
| Change from Baseline in MEG-derived Oscillatory Band Power | Baseline (pre-treatment) to 6 months post-treatment | Assessment of the longitudinal change in MEG-derived oscillatory band (delta, theta, alpha, beta, gamma) power over multiple time points. Unit of Measure: fT²/Hz, reported as average of differences |
| Change from Baseline in MEG-derived Network Coherence | Baseline (pre-treatment) to 6 months post-treatment | Assessment of the longitudinal change in MEG-derived network coherence over multiple time points. Unit of Measure: Unitless coherence index, reported as Z-score difference |
| Correlation between sonication energy and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between total sonication energy (Joules, J) and MEG-derived network measures including functional connectivity strength, directed connectivity, oscillatory band power, and network coherence. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Baseline (pre-treatment) to 6 months post-treatment | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between peak intra-procedural temperature (degrees Celsius, °C) and MEG-derived network measures including functional connectivity strength, directed connectivity, oscillatory band power, and network coherence. Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between number of sonications and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between the total number of sonications (count) and MEG-derived functional connectivity strength Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between lesion volume and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between lesion volume (cubic millimeters, mm³) and MEG-derived functional connectivity strength Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between patient age and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between patient age (years) and MEG-derived functional connectivity strength Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between disease duration and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between disease duration (years) and MEG-derived functional connectivity strength Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in CRST score and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in tremor severity as measured by the Clinical Rating Scale for Tremor (CRST score, points) and MEG-derived functional connectivity strength. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in tremor amplitude and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in wearable sensor-derived tremor amplitude (acceleration magnitude, m/s²) and MEG-derived functional connectivity strength. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in tremor frequency and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in tremor frequency (Hertz, Hz), measured using a wearable sensor and MEG-derived functional connectivity strength. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in gait speed and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in gait speed (meters per second, m/s) during a standardized walk test, obtained using wearable sensors and MEG-derived functional connectivity strength. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in postural sway and MEG connectivity | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in postural sway (acceleration magnitude, m/s²) from wearable sensors and MEG-derived functional connectivity strength. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
| Correlation between change from baseline in 360-degree turn performance and MEG-derived functional connectivity strength. | Baseline (pre-treatment) to 6 months post-treatment | Pearson correlation coefficient evaluating the relationship between change from baseline in 360-degree turn duration (seconds) and number of steps (count) from wearable sensors, and MEG-derived network measures. Unit of Measure: Correlation coefficient (r) ranging from -1 to 1 |
Contacts
CONTACTsubeikshanan venkatesan, MBBS
PRINCIPAL_INVESTIGATORJustin Hilliard, MD
University of Florida
Outcome results
None listed