Essential Tremor (ET)Phase 1/2LIFU-ETNCT07484152
Motor and Non-Motor Effects of Low-Intensity Focused Ultrasound (LIFU) as a Neuromodulation Tool in Essential Tremor
A Phase 1/2 study testing Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO in people with Essential Tremor (ET), run by University of Sao Paulo General Hospital.
Trial summary
This study investigates the motor and non-motor effects of Low-Intensity Focused Ultrasound (LIFU) as a non-invasive neuromodulation technique in patients with essential tremor (ET) and refractory tremor. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Essential Tremor (ET)
- What is being tested?
- Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 17 Mar 2026to 10 Dec 2028
- Phase
- Phase 1/2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of essencial Tremor.
- Presence of clinically relevant tremor despite optimized pharmacological treatment.3. Age 18-80 years.4. Ability and willingness to provide written informed consent.5. Availability to attend all scheduled study visits at HC-FMUSP.6. Availability of a brain MRI suitable for neuronavigation planning
Who cannot join
- 1. Dementia syndrome or severe cognitive impairment precluding informed consent or reliable clinical assessment.
- 2. Uncontrolled psychiatric disorders.3. Alcohol or illicit substance dependence.4. Use of stimulants or medications that lower seizure threshold.5. History of epileptic seizures within the last 6 months.6. Hospitalization or surgery within the last 6 months.7. Presence of implanted metallic or electronic devices in the cranium or spine that are contraindicated for focused ultrasound procedures (e.g., deep brain stimulator, cochlear implant, cardiac pacemaker, metal plates or wires).8. History of brain surgery or traumatic brain injury.9. Skull defects, craniotomy, or significant calvarial irregularities that preclude safe ultrasound delivery.10. Pregnancy or breastfeeding.11. Social impossibility of follow-up attendance.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Motor and Non-Motor Effects of Low-Intensity Focused Ultrasound (LIFU) as a Neuromodulation Tool in Movement Disorders: A Randomized, Double-Blind, Sham-Controlled, Crossover Clinical Trial in Essential Tremor
This study investigates the motor and non-motor effects of Low-Intensity Focused Ultrasound (LIFU) as a non-invasive neuromodulation technique in patients with essential tremor (ET) and refractory tremor. LIFU is a non-thermal, non-ablative form of transcranial focused ultrasound that modulates neural activity through mechanical mechanisms, including direct effects on neuronal membranes, alterations in membrane excitability, and modulation of synaptic transmission. Unlike high-intensity focused ultrasound (HIFU), which produces tissue ablation, LIFU induces reversible effects with a favorable safety profile, making it a promising candidate for non-invasive neuromodulation in movement disorders.
In this randomized, double-blind, sham-controlled, crossover trial, 20 patients with ET and refractory tremor will receive active LIFU targeting the ventral intermediate nucleus (VIM) of the thalamus and sham stimulation in separate sessions, separated by a washout period of at least 12 weeks. Clinical assessments using standardized and validated neurological scales will be performed before and after each session to evaluate changes in motor symptoms, tremor severity, quality of life, and non-motor features.
Read more
The primary outcome is the change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©). Secondary outcomes include the Patient Global Impression of Change (PGIC) and monitoring of adverse events.
This study is being conducted at the Movement Disorders Center of Hospital das Clínicas, University of São Paulo (HC-FMUSP), São Paulo, Brazil, and has been approved by the institutional ethics committee (CAPPesq; approval number 7.406.027).
Read the detailed description
Background: The most common cause of tremor is essential tremor (ET), a disorder characterized by action tremor that predominantly affects the upper limbs. It has a prevalence of approximately 1-2% in the general population, with increasing frequency with age. Pharmacological therapy is the mainstay of treatment, with propranolol and primidone considered first-line medications. Other drugs that may be used include topiramate, gabapentin, and alprazolam. Approximately 50% of patients do not achieve adequate symptom control with medications, either due to tremor severity or intolerance to adverse drug effects. Some refractory cases may benefit from bilateral deep brain stimulation (DBS) of the thalamus or unilateral thalamotomy, which can also be performed using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU). Although effective, these approaches are invasive or ablative, which may limit their applicability. Low-Intensity Focused Ultrasound (LIFU) offers a non-invasive, non-ablative alternative capable of modulating deep brain circuits transcranially with millimeter precision without causing permanent tissue damage. The ventral intermediate nucleus (VIM) of the thalamus is a well-established target for tremor reduction and has been validated in both DBS and HIFU thalamotomy studies. Study Design: Prospective, randomized, double-blind, sham-controlled, crossover clinical trial. Participants: Twenty adult patients with refractory essential tremor and clinically relevant tremor despite optimized pharmacological treatment will be included. Intervention: Each participant undergoes two study sessions (active LIFU and sham LIFU), assigned in random order and separated by a washout period of at least 12 weeks. The sequence is determined using computer-generated randomization (Randomizer.com) and is blinded to both participants and clinical assessors. LIFU Procedure: Stimulation is delivered using the NeuroFUS PRO device (Brainbox Ltd., Cardiff, UK), consisting of a 64 mm single-element focused ultrasound transducer coupled to the scalp using degassed aqueous ultrasound gel (Aquaflex, Parker Laboratories, USA). Targeting is performed using the Brainsight neuronavigation system (Rogue Research Inc., Montreal, Canada) based on each participant's individual MRI. The acoustic target is the ventral intermediate nucleus (VIM) of the thalamus, contralateral to the most affected side. Patient-specific acoustic simulations are performed prior to the procedure using MATLAB R2022a and the BRIC TUS Simulation Tools, incorporating individual MRI and CT data to model skull acoustic properties and adjust focal depth and trajectory. Stimulation Parameters: Transducer frequency: 500 kHz; pulse width: 5 ms; pulse repetition frequency (PRF): 10 Hz; duty cycle: 5%; maximum spatial-peak pulse-average intensity (ISPPA): 30 W/cm². The protocol consists of two applications of 10 minutes each, separated by a 20-minute interval. Each application includes 10 cycles of 30 seconds ON and 30 seconds OFF. Sham Condition: In the sham condition, the transducer is positioned identically to the active condition. The ultrasound generator is activated but delivers no acoustic energy to the brain. Auditory and physical sensations associated with the procedure are replicated to maintain participant blinding. Clinical Assessment: Validated neurological scales are administered immediately before and immediately after each stimulation session by a blinded evaluator following standardized assessment protocols. The scales include the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS), the Essential Tremor Rating Assessment Scale (TETRAS©), and the Patient Global Impression of Change (PGIC). Adverse events are also monitored after each session. A follow-up clinical reassessment is performed one month after each intervention.
- Conditions
- Essential Tremor (ET)
- Being tested
- Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO
- Keywords
- essential tremor
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRODevice
Also called LIFU, pulsed low-intensity focused ultrasound transcranial focused ultrasound, tFUS, TUS
Non-invasive transcranial neuromodulation using a focused ultrasound transducer (NeuroFUS PRO, Brainbox Ltd., UK) operating at 500 kHz. Pulsed ultrasound is delivered in two 10-minute applications separated by a 20-minute interval, targeting the VIM of the thalamus under MRI-based neuronavigation. Parameters: 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm².
Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRODevice
Also called LIFU, LIFUP, pulsed low-intensity focused ultrasound, transcranial focused ultrasound
Non-invasive transcranial neuromodulation using a focused ultrasound transducer (NeuroFUS PRO, Brainbox Ltd., UK) operating at 500 kHz. Pulsed ultrasound is delivered in two 10-minute applications separated by a 20-minute interval, targeting the VIM of the thalamus under MRI-based neuronavigation. Parameters: 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm²
| Study group | Role | What they receive |
|---|---|---|
| Active LIFU | Experimental | Participants receive transcranial Low-Intensity Focused Ultrasound (LIFU) targeting the ventral intermediate nucleus (VIM) of the thalamus, contralateral to the most affected side, delivered via the NeuroFUS PRO device (Brainbox Ltd., UK) with the following parameters: 500 kHz frequency, 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm². Each session consists of two 10-minute sonication blocks separated by a 20-minute interval, guided by individual MRI-based neuronavigation (Brainsight, Rogue Research). Receives: Device: Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO |
| Sham LIFU | Sham comparator | Participants undergo an identical procedure including transducer positioning, neuronavigation guidance, and full session duration, but no ultrasound energy is delivered to the brain. The sham condition replicates the auditory and tactile sensations of the active condition to maintain participant blinding. Receives: Device: Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©).
Fahn-Tolosa-Marín (FTM) Tremor Rating Scale Total Score is a validated scale assessing tremor severity, including tremor amplitude, functional disability, and impact on activities of daily living across multiple body regions. The total score ranges from 0 to 144, with higher scores indicating greater tremor severity.
Essential Tremor Rating Assessment Scale (TETRAS) Total Score is a validated scale designed specifically for Essential Tremor, assessing tremor severity and functional disability. Higher scores indicate greater tremor severity. The total score ranges from 0 to 112, with with higher scores indicating greater tremor severity.
Measured: Baseline (immediately pre-stimulation) and immediately after the LIFU/sham session, at Week 0 (Phase 1) and Week 12 (Phase 2); and at 4 weeks post-stimulation (Week 4 and Week 16)
Secondary outcomes (1)
Application of the Patient Global Impression of Change (PGIC) and assessment of the number and type of adverse events
Application of the Patient Global Impression of Change to assess the participant's overall perception of improvement or worsening of tremor symptoms following the intervention and assessment of the number and type of adverse events occurring during the study period to evaluate the safety of the intervention.
Measured: In post-stimulation and 4 weeks post-stimulation at each phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start17 Mar 2026 (estimated)
- Primary completion10 May 2028 (estimated)
- Study completion10 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Essential Tremor (ET)Studies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant receives both active LIFU and sham LIFU in a randomized order, separated by an 12-week washout period. The crossover design allows each participant to serve as their own control (20 active vs. 20 sham comparisons).
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rubens Gisbert Cury, Principal investigator, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Movement Disorders Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07484152
- Sponsor's protocol ID
- CAAE 63579822.3.0000.0068
- Other IDs
- 7.406.027
- Acronym
- LIFU-ET
- Status last verified
- Mar 2026
- First submitted
- 16 Mar 2026
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vuong MQ, Sreenivasan V, Lee S, Quinn B, Keung MS, Grundy M, Ayala Castaneda J, Baek H, McKeown MJ. Low-intensity transcranial ultrasound effects on the ventral intermediate nucleus and zona incerta in Parkinson's disease tremor. Brain Stimul. 2026 Jan-Feb;19(1):103025. doi: 10.1016/j.brs.2026.103025. Epub 2026 Jan 8.
PubMed 41519465Sharabi S, Daniels D, Last D, Guez D, Zivli Z, Castel D, Levy Y, Volovick A, Grinfeld J, Rachmilevich I, Amar T, Mardor Y, Harnof S. Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model. Brain Stimul. 2019 Jan-Feb;12(1):1-8. doi: 10.1016/j.brs.2018.08.014. Epub 2018 Aug 27.
PubMed 30181107Legon W, Adams S, Bansal P, Patel PD, Hobbs L, Ai L, Mueller JK, Meekins G, Gillick BT. A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Sci Rep. 2020 Mar 27;10(1):5573. doi: 10.1038/s41598-020-62265-8.
PubMed 32221350Fomenko A, Neudorfer C, Dallapiazza RF, Kalia SK, Lozano AM. Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Brain Stimul. 2018 Nov-Dec;11(6):1209-1217. doi: 10.1016/j.brs.2018.08.013. Epub 2018 Aug 23.
PubMed 30166265Meng Y, Hynynen K, Lipsman N. Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nat Rev Neurol. 2021 Jan;17(1):7-22. doi: 10.1038/s41582-020-00418-z. Epub 2020 Oct 26.
PubMed 33106619Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB, Huss D, Dallapiazza RF, Gwinn R, Witt J, Ro S, Eisenberg HM, Fishman PS, Gandhi D, Halpern CH, Chuang R, Butts Pauly K, Tierney TS, Hayes MT, Cosgrove GR, Yamaguchi T, Abe K, Taira T, Chang JW. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016 Aug 25;375(8):730-9. doi: 10.1056/NEJMoa1600159.
PubMed 27557301Shah C, Jackson GR, Sarwar AI, Mandava P, Jamal F. Treatment Patterns in Essential Tremor: A Retrospective Analysis. Tremor Other Hyperkinet Mov (N Y). 2022 Mar 23;12:10. doi: 10.5334/tohm.682. eCollection 2022.
PubMed 35415009
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Motor and Non-Motor Effects of Low-Intensity Focused Ultrasound (LIFU) as a Neuromodulation Tool in Movement Disorders: A Randomized, Double-Blind, Sham-Controlled, Crossover Clinical Trial in Essential Tremor
- ClinicalTrials.gov ID
- NCT07484152
- Acronym / sponsor ID
- LIFU-ET / CAAE 63579822.3.0000.0068
- Conditions
- Essential Tremor (ET)
- Keywords
- essential tremor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- 17 Mar 2026 (estimated)
- Primary completion
- 10 May 2028 (estimated)
- Study completion
- 10 Dec 2028 (estimated)
- First posted
- 19 Mar 2026 (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.
This study investigates the motor and non-motor effects of Low-Intensity Focused Ultrasound (LIFU) as a non-invasive neuromodulation technique in patients with essential tremor (ET) and refractory tremor. LIFU is a non-thermal, non-ablative form of transcranial focused ultrasound that modulates neural activity through mechanical mechanisms, including direct effects on neuronal membranes, alterations in membrane excitability, and modulation of synaptic transmission. Unlike high-intensity focused ultrasound (HIFU), which produces tissue ablation, LIFU induces reversible effects with a favorable safety profile, making it a promising candidate for non-invasive neuromodulation in movement disorders.
In this randomized, double-blind, sham-controlled, crossover trial, 20 patients with ET and refractory tremor will receive active LIFU targeting the ventral intermediate nucleus (VIM) of the thalamus and sham stimulation in separate sessions, separated by a washout period of at least 12 weeks. Clinical assessments using standardized and validated neurological scales will be performed before and after each session to evaluate changes in motor symptoms, tremor severity, quality of life, and non-motor features.
The primary outcome is the change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©). Secondary outcomes include the Patient Global Impression of Change (PGIC) and monitoring of adverse events.
This study is being conducted at the Movement Disorders Center of Hospital das Clínicas, University of São Paulo (HC-FMUSP), São Paulo, Brazil, and has been approved by the institutional ethics committee (CAPPesq; approval number 7.406.027).
Detailed description
Background: The most common cause of tremor is essential tremor (ET), a disorder characterized by action tremor that predominantly affects the upper limbs. It has a prevalence of approximately 1-2% in the general population, with increasing frequency with age. Pharmacological therapy is the mainstay of treatment, with propranolol and primidone considered first-line medications. Other drugs that may be used include topiramate, gabapentin, and alprazolam. Approximately 50% of patients do not achieve adequate symptom control with medications, either due to tremor severity or intolerance to adverse drug effects. Some refractory cases may benefit from bilateral deep brain stimulation (DBS) of the thalamus or unilateral thalamotomy, which can also be performed using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU). Although effective, these approaches are invasive or ablative, which may limit their applicability. Low-Intensity Focused Ultrasound (LIFU) offers a non-invasive, non-ablative alternative capable of modulating deep brain circuits transcranially with millimeter precision without causing permanent tissue damage. The ventral intermediate nucleus (VIM) of the thalamus is a well-established target for tremor reduction and has been validated in both DBS and HIFU thalamotomy studies. Study Design: Prospective, randomized, double-blind, sham-controlled, crossover clinical trial. Participants: Twenty adult patients with refractory essential tremor and clinically relevant tremor despite optimized pharmacological treatment will be included. Intervention: Each participant undergoes two study sessions (active LIFU and sham LIFU), assigned in random order and separated by a washout period of at least 12 weeks. The sequence is determined using computer-generated randomization (Randomizer.com) and is blinded to both participants and clinical assessors. LIFU Procedure: Stimulation is delivered using the NeuroFUS PRO device (Brainbox Ltd., Cardiff, UK), consisting of a 64 mm single-element focused ultrasound transducer coupled to the scalp using degassed aqueous ultrasound gel (Aquaflex, Parker Laboratories, USA). Targeting is performed using the Brainsight neuronavigation system (Rogue Research Inc., Montreal, Canada) based on each participant's individual MRI. The acoustic target is the ventral intermediate nucleus (VIM) of the thalamus, contralateral to the most affected side. Patient-specific acoustic simulations are performed prior to the procedure using MATLAB R2022a and the BRIC TUS Simulation Tools, incorporating individual MRI and CT data to model skull acoustic properties and adjust focal depth and trajectory. Stimulation Parameters: Transducer frequency: 500 kHz; pulse width: 5 ms; pulse repetition frequency (PRF): 10 Hz; duty cycle: 5%; maximum spatial-peak pulse-average intensity (ISPPA): 30 W/cm². The protocol consists of two applications of 10 minutes each, separated by a 20-minute interval. Each application includes 10 cycles of 30 seconds ON and 30 seconds OFF. Sham Condition: In the sham condition, the transducer is positioned identically to the active condition. The ultrasound generator is activated but delivers no acoustic energy to the brain. Auditory and physical sensations associated with the procedure are replicated to maintain participant blinding. Clinical Assessment: Validated neurological scales are administered immediately before and immediately after each stimulation session by a blinded evaluator following standardized assessment protocols. The scales include the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS), the Essential Tremor Rating Assessment Scale (TETRAS©), and the Patient Global Impression of Change (PGIC). Adverse events are also monitored after each session. A follow-up clinical reassessment is performed one month after each intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Each participant receives both active LIFU and sham LIFU in a randomized order, separated by an 12-week washout period. The crossover design allows each participant to serve as their own control (20 active vs. 20 sham comparisons).
| Arm | Type | Receives |
|---|---|---|
| Active LIFU | Experimental | Device: Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PROParticipants receive transcranial Low-Intensity Focused Ultrasound (LIFU) targeting the ventral intermediate nucleus (VIM) of the thalamus, contralateral to the most affected side, delivered via the NeuroFUS PRO device (Brainbox Ltd., UK) with the following parameters: 500 kHz frequency, 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm². Each session consists of two 10-minute sonication blocks separated by a 20-minute interval, guided by individual MRI-based neuronavigation (Brainsight, Rogue Research). |
| Sham LIFU | Sham comparator | Device: Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PROParticipants undergo an identical procedure including transducer positioning, neuronavigation guidance, and full session duration, but no ultrasound energy is delivered to the brain. The sham condition replicates the auditory and tactile sensations of the active condition to maintain participant blinding. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of essencial Tremor.
- Presence of clinically relevant tremor despite optimized pharmacological treatment.3. Age 18-80 years.4. Ability and willingness to provide written informed consent.5. Availability to attend all scheduled study visits at HC-FMUSP.6. Availability of a brain MRI suitable for neuronavigation planning
Key exclusion criteria (2 listed)
- 1. Dementia syndrome or severe cognitive impairment precluding informed consent or reliable clinical assessment.
- 2. Uncontrolled psychiatric disorders.3. Alcohol or illicit substance dependence.4. Use of stimulants or medications that lower seizure threshold.5. History of epileptic seizures within the last 6 months.6. Hospitalization or surgery within the last 6 months.7. Presence of implanted metallic or electronic devices in the cranium or spine that are contraindicated for focused ultrasound procedures (e.g., deep brain stimulator, cochlear implant, cardiac pacemaker, metal plates or wires).8. History of brain surgery or traumatic brain injury.9. Skull defects, craniotomy, or significant calvarial irregularities that preclude safe ultrasound delivery.10. Pregnancy or breastfeeding.11. Social impossibility of follow-up attendance.
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 Ultrasound (LIFU) - NeuroFUS PROAlso: LIFU, pulsed low-intensity focused ultrasound transcranial focused ultrasound, tFUS, TUSNon-invasive transcranial neuromodulation using a focused ultrasound transducer (NeuroFUS PRO, Brainbox Ltd., UK) operating at 500 kHz. Pulsed ultrasound is delivered in two 10-minute applications separated by a 20-minute interval, targeting the VIM of the thalamus under MRI-based neuronavigation. Parameters: 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm². | Device | Active LIFU |
| Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PROAlso: LIFU, LIFUP, pulsed low-intensity focused ultrasound, transcranial focused ultrasoundNon-invasive transcranial neuromodulation using a focused ultrasound transducer (NeuroFUS PRO, Brainbox Ltd., UK) operating at 500 kHz. Pulsed ultrasound is delivered in two 10-minute applications separated by a 20-minute interval, targeting the VIM of the thalamus under MRI-based neuronavigation. Parameters: 5 ms pulse width, 10 Hz PRF, 5% duty cycle, ISPPA 30 W/cm² | Device | Sham LIFU |
Primary outcome
Change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©).
Time frame: Baseline (immediately pre-stimulation) and immediately after the LIFU/sham session, at Week 0 (Phase 1) and Week 12 (Phase 2); and at 4 weeks post-stimulation (Week 4 and Week 16)
Fahn-Tolosa-Marín (FTM) Tremor Rating Scale Total Score is a validated scale assessing tremor severity, including tremor amplitude, functional disability, and impact on activities of daily living across multiple body regions. The total score ranges from 0 to 144, with higher scores indicating greater tremor severity. Essential Tremor Rating Assessment Scale (TETRAS) Total Score is a validated scale designed specifically for Essential Tremor, assessing tremor severity and functional disability. Higher scores indicate greater tremor severity. The total score ranges from 0 to 112, with with higher scores indicating greater tremor severity.
1 secondary outcome
Application of the Patient Global Impression of Change (PGIC) and assessment of the number and type of adverse events
Time frame: In post-stimulation and 4 weeks post-stimulation at each phase
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 19 Mar 2026.
- Background: PubMed 41519465Vuong MQ, Sreenivasan V, Lee S, Quinn B, Keung MS, Grundy M, Ayala Castaneda J, Baek H, McKeown MJ. Low-intensity transcranial ultrasound effects on the ventral intermediate nucleus and zona incerta in Parkinson's disease tremor. Brain Stimul. 2026 Jan-Feb;19(1):103025. doi: 10.1016/j.brs.2026.103025. Epub 2026 Jan 8.
- Background: PubMed 30181107Sharabi S, Daniels D, Last D, Guez D, Zivli Z, Castel D, Levy Y, Volovick A, Grinfeld J, Rachmilevich I, Amar T, Mardor Y, Harnof S. Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model. Brain Stimul. 2019 Jan-Feb;12(1):1-8. doi: 10.1016/j.brs.2018.08.014. Epub 2018 Aug 27.
- Background: PubMed 32221350Legon W, Adams S, Bansal P, Patel PD, Hobbs L, Ai L, Mueller JK, Meekins G, Gillick BT. A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. Sci Rep. 2020 Mar 27;10(1):5573. doi: 10.1038/s41598-020-62265-8.
- Background: PubMed 30166265Fomenko A, Neudorfer C, Dallapiazza RF, Kalia SK, Lozano AM. Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications. Brain Stimul. 2018 Nov-Dec;11(6):1209-1217. doi: 10.1016/j.brs.2018.08.013. Epub 2018 Aug 23.
- Background: PubMed 33106619Meng Y, Hynynen K, Lipsman N. Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nat Rev Neurol. 2021 Jan;17(1):7-22. doi: 10.1038/s41582-020-00418-z. Epub 2020 Oct 26.
- Background: PubMed 27557301Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB, Huss D, Dallapiazza RF, Gwinn R, Witt J, Ro S, Eisenberg HM, Fishman PS, Gandhi D, Halpern CH, Chuang R, Butts Pauly K, Tierney TS, Hayes MT, Cosgrove GR, Yamaguchi T, Abe K, Taira T, Chang JW. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016 Aug 25;375(8):730-9. doi: 10.1056/NEJMoa1600159.
- Background: PubMed 35415009Shah C, Jackson GR, Sarwar AI, Mandava P, Jamal F. Treatment Patterns in Essential Tremor: A Retrospective Analysis. Tremor Other Hyperkinet Mov (N Y). 2022 Mar 23;12:10. doi: 10.5334/tohm.682. eCollection 2022.
- Individual participant dataSharing planned: Undecided
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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.
Rubens Gisbert Cury principal investigator
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Movement Disorders Center
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low-Intensity Focused Ultrasound (LIFU) - NeuroFUS PRO in people with Essential Tremor (ET), run by University of Sao Paulo General Hospital.
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 2 inclusion and 2 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: opening soon, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Rubens Gisbert Cury (+55 11 2661-7877, rubens_cury@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©). (time frame: Baseline (immediately pre-stimulation) and immediately after the LIFU/sham session, at Week 0 (Phase 1) and Week 12 (Phase 2); and at 4 weeks post-stimulation (Week 4 and Week 16)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07484152, which also lists 7 linked publications.
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 19 Mar 2026.