Essential TremorPhase 1/2NCT07344194
Dual-Site Transcranial Magnetic Stimulation of the Supplementary Motor Area and Cerebellum for the Treatment of Essential Tremor.
A Phase 1/2 study testing Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellum in people with Essential Tremor, run by São Paulo State University at 1 site in Brazil.
Trial summary
Essential tremor is a common movement disorder that causes involuntary shaking, mainly during voluntary actions such as writing or holding objects. Recent research suggests that essential tremor is not caused by a single brain area, but by abnormal activity within a network that includes the cerebellum and motor areas… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Essential Tremor
- What is being tested?
- Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellum
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Jan 2026to Jan 2027
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female participants, aged 18 to 80 years; women of childbearing potential must not be pregnant.
- Diagnosis of Essential Tremor with a score greater than 2 on items 5 or 6 of the Fahn-Tolosa-Marin Tremor Rating Scale despite optimized medical therapy.
- Medication-refractory tremor, defined as prior use of both first-line medications (propranolol and primidone) at maximally tolerated doses without adequate tremor control.
- Ability to provide written informed consent in accordance with institutional policies.
- Ability to comply with all study procedures and follow-up assessments as defined by the study protocol.
Who cannot join
- Unstable or untreated psychiatric disorders.
- Inability to provide informed consent.
- Uncontrolled medical conditions, including but not limited to uncontrolled diabetes mellitus, hypertension, symptomatic pulmonary disease, or symptomatic cardiac disease.
- Concomitant participation in another investigational drug or device study.
- Pregnancy or breastfeeding.
- Presence of an implanted deep brain stimulation (DBS) system.
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- History of epilepsy not adequately controlled, defined as seizure-free for less than 5 years.
- Presence of a cardiac pacemaker.
- Presence of metallic implants in any part of the body that are contraindicated for rTMS.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Sao Paulo University
São Paulo, São Paulo, 05414-025
ANANDA CAROLINA MORAES DE FALCONE, 16981768412, ananda.falcone@alumni.usp.br
About this study
Official title: Dual-Site Transcranial Magnetic Stimulation of the Supplementary Motor Area and Cerebellum for the Treatment of Essential Tremor
Essential tremor is a common movement disorder that causes involuntary shaking, mainly during voluntary actions such as writing or holding objects. Recent research suggests that essential tremor is not caused by a single brain area, but by abnormal activity within a network that includes the cerebellum and motor areas of the brain. However, most non-invasive brain stimulation studies to date have targeted only one brain region and have shown inconsistent clinical benefits.
This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of a dual-site transcranial magnetic stimulation (rTMS) protocol targeting the supplementary motor area (SMA) and the cerebellum in patients with essential tremor that does not respond adequately to standard medications. The study is based on previous pilot data showing meaningful tremor reduction using combined stimulation of these two brain regions.
Participants will receive five sessions of rTMS, consisting of low-frequency stimulation over the SMA followed by high-frequency stimulation over the cerebellum. The main hypothesis is that this combined approach will lead to an immediate and sustained improvement in action tremor of the dominant upper limb, measured up to four weeks after treatment. Secondary outcomes include quality of life, safety, side effects, and changes in brain excitability associated with tremor improvement.
Read the detailed description
This study is a randomized, double-blind, placebo-controlled, parallel-group phase II clinical trial designed to investigate the effects of dual-site repetitive transcranial magnetic stimulation (rTMS) in patients with medication-refractory essential tremor. The trial is conducted at the University of São Paulo.
Participants are randomized to receive either active or sham stimulation over five consecutive daily sessions. The active intervention consists of sequential stimulation of two interconnected nodes of the tremor network. Low-frequency rTMS (1 Hz, 110% of resting motor threshold) is first applied over the supplementary motor area in 24 trains with 3-second inter-train intervals, followed by high-frequency stimulation of the cerebellar cortex (10 Hz, 90% of resting motor threshold) delivered in 12 trains with 3-second inter-train intervals. The protocol is designed to modulate cortical motor drive and cerebellar output within the cerebello-thalamo-cortical circuit.
The stimulation parameters and dual-site approach were selected based on neurophysiological and neuroimaging evidence supporting a network-based model of essential tremor, as well as on pilot data demonstrating clinically meaningful tremor reduction following combined stimulation of the supplementary motor area and cerebellum.
Participants are evaluated at baseline, immediately after completion of the stimulation protocol, and during follow-up to assess clinical effects, safety, and neurophysiological changes associated with the intervention. This study aims to further characterize the therapeutic potential of network-targeted rTMS in essential tremor and to inform future neuromodulation strategies in this population.
- Conditions
- Essential Tremor
- Being tested
- Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellum, Transcranial Magnetic Stimulation Sham
- Keywords
- essential tremor, rTMS, movement disorders, non-invasive neuromodulation
- Medical subject headings
- Essential Tremor, Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellumDevice
This intervention consists of a sequential dual-site repetitive transcranial magnetic stimulation (rTMS) protocol targeting two interconnected nodes of the tremor network. Low-frequency stimulation (1 Hz) is first applied over the supplementary motor area at 110% of the resting motor threshold to modulate cortical motor drive, followed by high-frequency stimulation (10 Hz) over the cerebellar cortex at 90% of the resting motor threshold to modulate abnormal cerebellar output. Stimulation is delivered over five consecutive daily sessions using standardized anatomical localization and identical session duration across participants.
Sham Intervention
The sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar cortex
Transcranial Magnetic Stimulation ShamDevice
Also called Sham
The sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar targets, while sound simulation is used to mimic active stimulation, ensuring maintenance of blinding and comparability with the active intervention.
| Study group | Role | What they receive |
|---|---|---|
| Dual-site rTMS over SMA (1 Hz, 110% RMT) and cerebellum (10 Hz, 90% RMT) for 5 days. | Experimental | Sham stimulation over SMA and cerebellum using inactive coil with sound simulation for 5 days. Receives: Device: Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellum |
| Sham | Sham comparator | The sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar targets, while sound simulation is used to mimic active stimulation, ensuring maintenance of blinding and comparability with the active intervention. Receives: Device: Transcranial Magnetic Stimulation Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Action Tremor Severity of the Dominant Upper Limb
Assessed using items 5 and 6 of the Fahn-Tolosa-Marin Tremor Rating Scale, evaluated by a blinded examiner.
Measured: baseline (pre-stimulation), at the end of the stimulation protocol, 4 weeks after the last session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2026
- Study start15 Jan 2026
- Primary completionOct 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential TremorStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention is active rTMS stimulation (1 Hz, 110% of resting motor threshold) over the supplementary motor area in 24 trains with 3-second inter-train intervals, followed by high-frequency stimulation of the cerebellar cortex (10 Hz, 90% of resting motor threshold) delivered in 12 trains with 3-second inter-train intervals
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- São Paulo State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ANANDA CAROLINA MORAES DE FALCONE, São Paulo State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07344194
- Sponsor's protocol ID
- 81190724.8.0000.0068
- Status last verified
- Jan 2026
- First submitted
- 7 Jan 2026
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in publications will be made available upon reasonable request to the corresponding author, following publication. Data sharing will be subject to approval by the institutional ethics committee and execution of a data use agreement, in accordance with applicable data protection regulations.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual-Site Transcranial Magnetic Stimulation of the Supplementary Motor Area and Cerebellum for the Treatment of Essential Tremor
- ClinicalTrials.gov ID
- NCT07344194
- Acronym / sponsor ID
- 81190724.8.0000.0068
- Conditions
- Essential Tremor
- Keywords
- essential tremor, rTMS, movement disorders, non-invasive neuromodulation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- São Paulo State UniversityUniversity, hospital or other
- Study start
- 15 Jan 2026 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 15 Jan 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.
Essential tremor is a common movement disorder that causes involuntary shaking, mainly during voluntary actions such as writing or holding objects. Recent research suggests that essential tremor is not caused by a single brain area, but by abnormal activity within a network that includes the cerebellum and motor areas of the brain. However, most non-invasive brain stimulation studies to date have targeted only one brain region and have shown inconsistent clinical benefits.
This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of a dual-site transcranial magnetic stimulation (rTMS) protocol targeting the supplementary motor area (SMA) and the cerebellum in patients with essential tremor that does not respond adequately to standard medications. The study is based on previous pilot data showing meaningful tremor reduction using combined stimulation of these two brain regions.
Participants will receive five sessions of rTMS, consisting of low-frequency stimulation over the SMA followed by high-frequency stimulation over the cerebellum. The main hypothesis is that this combined approach will lead to an immediate and sustained improvement in action tremor of the dominant upper limb, measured up to four weeks after treatment. Secondary outcomes include quality of life, safety, side effects, and changes in brain excitability associated with tremor improvement.
Detailed description
This study is a randomized, double-blind, placebo-controlled, parallel-group phase II clinical trial designed to investigate the effects of dual-site repetitive transcranial magnetic stimulation (rTMS) in patients with medication-refractory essential tremor. The trial is conducted at the University of São Paulo.
Participants are randomized to receive either active or sham stimulation over five consecutive daily sessions. The active intervention consists of sequential stimulation of two interconnected nodes of the tremor network. Low-frequency rTMS (1 Hz, 110% of resting motor threshold) is first applied over the supplementary motor area in 24 trains with 3-second inter-train intervals, followed by high-frequency stimulation of the cerebellar cortex (10 Hz, 90% of resting motor threshold) delivered in 12 trains with 3-second inter-train intervals. The protocol is designed to modulate cortical motor drive and cerebellar output within the cerebello-thalamo-cortical circuit.
The stimulation parameters and dual-site approach were selected based on neurophysiological and neuroimaging evidence supporting a network-based model of essential tremor, as well as on pilot data demonstrating clinically meaningful tremor reduction following combined stimulation of the supplementary motor area and cerebellum.
Participants are evaluated at baseline, immediately after completion of the stimulation protocol, and during follow-up to assess clinical effects, safety, and neurophysiological changes associated with the intervention. This study aims to further characterize the therapeutic potential of network-targeted rTMS in essential tremor and to inform future neuromodulation strategies in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- The intervention is active rTMS stimulation (1 Hz, 110% of resting motor threshold) over the supplementary motor area in 24 trains with 3-second inter-train intervals, followed by high-frequency stimulation of the cerebellar cortex (10 Hz, 90% of resting motor threshold) delivered in 12 trains with 3-second inter-train intervals
| Arm | Type | Receives |
|---|---|---|
| Dual-site rTMS over SMA (1 Hz, 110% RMT) and cerebellum (10 Hz, 90% RMT) for 5 days. | Experimental | Device: Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellumSham stimulation over SMA and cerebellum using inactive coil with sound simulation for 5 days. |
| Sham | Sham comparator | Device: Transcranial Magnetic Stimulation ShamThe sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar targets, while sound simulation is used to mimic active stimulation, ensuring maintenance of blinding and comparability with the active intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female participants, aged 18 to 80 years; women of childbearing potential must not be pregnant.
- Diagnosis of Essential Tremor with a score greater than 2 on items 5 or 6 of the Fahn-Tolosa-Marin Tremor Rating Scale despite optimized medical therapy.
- Medication-refractory tremor, defined as prior use of both first-line medications (propranolol and primidone) at maximally tolerated doses without adequate tremor control.
- Ability to provide written informed consent in accordance with institutional policies.
- Ability to comply with all study procedures and follow-up assessments as defined by the study protocol.
Key exclusion criteria (9 listed)
- Unstable or untreated psychiatric disorders.
- Inability to provide informed consent.
- Uncontrolled medical conditions, including but not limited to uncontrolled diabetes mellitus, hypertension, symptomatic pulmonary disease, or symptomatic cardiac disease.
- Concomitant participation in another investigational drug or device study.
- Pregnancy or breastfeeding.
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 |
|---|---|---|
| Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellumThis intervention consists of a sequential dual-site repetitive transcranial magnetic stimulation (rTMS) protocol targeting two interconnected nodes of the tremor network. Low-frequency stimulation (1 Hz) is first applied over the supplementary motor area at 110% of the resting motor threshold to modulate cortical motor drive, followed by high-frequency stimulation (10 Hz) over the cerebellar cortex at 90% of the resting motor threshold to modulate abnormal cerebellar output. Stimulation is delivered over five consecutive daily sessions using standardized anatomical localization and identical session duration across participants. Sham Intervention The sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar cortex | Device | Dual-site rTMS over SMA (1 Hz, 110% RMT) and cerebellum (10 Hz, 90% RMT) for 5 days. |
| Transcranial Magnetic Stimulation ShamAlso: ShamThe sham intervention replicates the anatomical targeting, sequence, session duration, and acoustic characteristics of the active dual-site rTMS protocol without delivering an effective magnetic field. An inactive coil is positioned over the same supplementary motor area and cerebellar targets, while sound simulation is used to mimic active stimulation, ensuring maintenance of blinding and comparability with the active intervention. | Device | Sham |
Primary outcome
Change in Action Tremor Severity of the Dominant Upper Limb
Time frame: baseline (pre-stimulation), at the end of the stimulation protocol, 4 weeks after the last session
Assessed using items 5 and 6 of the Fahn-Tolosa-Marin Tremor Rating Scale, evaluated by a blinded examiner.
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 21 Jan 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in publications will be made available upon reasonable request to the corresponding author, following publication. Data sharing will be subject to approval by the institutional ethics committee and execution of a data use agreement, in accordance with applicable data protection regulations.
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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 Phase 1/2 study testing Dual-site repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area and cerebellum in people with Essential Tremor, run by São Paulo State University at 1 site in Brazil.
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 5 inclusion and 9 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 21 Jan 2026. 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 Brazil. 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. 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 ANANDA CAROLINA MORAES DE FALCONE, MD (+5516981768412, ananda.falcone@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Action Tremor Severity of the Dominant Upper Limb (time frame: baseline (pre-stimulation), at the end of the stimulation protocol, 4 weeks after the last session). 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 21 Jan 2026.