Orthostatic TremorLIFUS-POTNCT05547620
Modulating Cerebellar Activity With Low-intensity Focused Ultrasound Stimulation for Primary Orthostatic Tremor
A study testing LIFUS Online Real and LIFUS Offline in people with Orthostatic Tremor, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Primary orthostatic tremor (POT) is a rare movement disorder that is manifested through high frequency tremor of weight bearing limbs. This is often accompanied by a debilitating sensation of falling. POT has been linked to abnormal activity of the cerebellum, a structure deep within the brain. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Orthostatic Tremor
- What is being tested?
- LIFUS Online Real and LIFUS Offline
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 8 Mar 2021to Sep 2027
- Phase
- Interventional
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-90 years of age
- Confirmed diagnosis of orthostatic tremor
Who cannot join
- History of stroke or seizure
- Comorbid dementia
- Scored below 22 on the Montreal Cognitive Assessment (MoCA)
- Has intracranial implant(s) or device(s)
- Has an implanted cardiac pacemaker or implantable cardioverter-defibrillator (ICD)
- Has a previous surgical intervention to treat the movement disorder such as lesioning or a deep brain stimulation (DBS) system in place.
Show all 12Show fewer
- Presence of metal implanted in body that is contraindicated in TMS/MRI
- Pregnancy
- Major depression/psychiatric disorder that in the opinion of the Investigator will affect patient's understanding of study procedures and willingness to abide by all procedures during the course of the study
- Is on antipsychotics, marijuana, or other recreational drugs that affect the nervous system
- Major musculoskeletal or neuromuscular disease or disorder of the hands, wrists and limbs
- Major systemic illness or infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Modulating Dysfunctional Cerebellar Activity With Low-intensity Focused Ultrasound Stimulation for Primary Orthostatic Tremor
Primary orthostatic tremor (POT) is a rare movement disorder that is manifested through high frequency tremor of weight bearing limbs. This is often accompanied by a debilitating sensation of falling. POT has been linked to abnormal activity of the cerebellum, a structure deep within the brain. However, established non-invasive brain stimulation techniques can only modulate brain activity and plasticity in superficial brain areas with low spatial resolution. This limits their efficacy when targeting the cerebellum. In contrast, low intensity focused ultrasound (LIFUS) is a novel non-invasive brain stimulation technique that permits stimulation with high spatial focality and can reach greater depth compared other methods. Therefore, LIFUS is well suited to modulate cerebellar activity and has the potential to be a superior technique for the management of POT. This study will investigate the effectiveness of MRI-guided bilateral cerebellar LIFUS stimulation for the treatment of POT and evaluate the underlying changes in brain circuits caused by the stimulation. Comparisons between symptoms and connectivity of brain circuits pre- and post-stimulation will be conducted to assess the effects of cerebellar LIFUS. The effects of real stimulation will also be compared to sham stimulation. This study is the first to apply LIFUS for neuromodulation in POT and will be critical in developing therapeutic LIFUS protocols.
Read the detailed description
In the current study the investigators aim to assess the effects of low intensity focused ultrasound (LIFUS) on the symptoms of primary orthostatic tremor (POT) and on brain connectivity. LIFUS is a promising non-invasive brain stimulation technique that is actively being studied for its ability to reversibly modulate brain activity. By focusing the propagation of acoustic wave through the skull, a higher degree of spatial specificity and deep targeting can be achieved over other non-invasive stimulation methods such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). Specifically, investigators will use LIFUS to stimulate the cerebellum bilaterally for 80s per hemisphere using a theta burst protocol that investigators have shown to induce plasticity. Investigators hypothesize that modulating cerebellar activity will decrease symptoms of POT and normalize the dysfunctional cerebello-thalamo-cortico network. 15 POT patients will be recruited to participate in 3 sessions in-lab. The first visit will involve an anatomical magnetic resonance image (MRI) scan. This will allow us to accurately target cerebellar lobule VIII and establish the appropriate parameters of LIFUS to effectively pass through the skull. In visits 2 and 3 participants will be seated in a comfortable chair and an anatomical MRI image will be used to position the LIFUS transducer over cerebellar lobule VIII bilaterally on surface of their head. In visit 2, clinical assessments of POT will be conducted through electromyography (EMG) recordings and video analysis of posture and sway. Symptoms prior to and after LIFUS will be compared. Investigators will compare the effects of real stimulation to a sham stimulation. In visit 3, Investigators will assess brain network activity using transcranial magnetic stimulation (TMS) by employing an established paired-pulse paradigm. This method will allow us to establish the effects of LIFUS on the cerebello-thalamo-cortical network and determine how this related to changes observed in POT symptoms.
- Conditions
- Orthostatic Tremor
- Being tested
- LIFUS Online Real, LIFUS Online Sham, LIFUS Offline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LIFUS Online RealDevice
Stimulation using NeuroFUS device while standing
LIFUS Online ShamDevice
Stimulation using NeuroFUS device while standing
LIFUS OfflineDevice
Stimulation using NeuroFUS device prior to standing
| Study group | Role | What they receive |
|---|---|---|
| Low Intensity Focused ultrasound | Experimental | NeuroFUS device stimulation with 4 channel transducer Stimulation target = Cerebellum Receives: Device: LIFUS Online Real; Device: LIFUS Online Sham; Device: LIFUS Offline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tremor frequency
The primary outcomes will consist of peak tremor frequency recorded from surface electromyography (EMG). The EMG electrodes will be placed on the skin, and electrical activity produced by muscle contractions will be recorded. From the recordings of EMGs, peak frequency will be extracted through statistical analyses.
Measured: 2 Years
Power spectral analysis
Power spectrum recorded from surface electromyography (EMG). The EMG electrodes will be placed on the skin, and electrical activity produced by muscle contractions will be recorded. From the recordings of EMGs, power spectrum will be extracted through statistical analyses.
Measured: 2 Years
Orthostatic Tremor Severity and Disability Scale (OT-10)
The Orthostatic Tremor Severity and Disability Scale (OT-10) is a self-administered 10-item scale that measures the severity and disability of orthostatic tremor. Each item is rated from 0-5, with higher scores representing worse outcome.
Measured: 2 Years
Secondary outcomes (2)
Assessment of body posture
Posture during standing will be video recorded and analyzed using Kinovea, an analysis software for evaluation of human movements that express measurements in figures, tables, and graphics. Specifically, posture analysis will be carried out by measuring the alignment of the head, shoulder, hips, knees, and ankles. Deviation scores for each alignment measure will be calculated and averaged to calculate an overall alignment deviation score for each participant.
Measured: 2 Years
Standing time
Duration of standing
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start8 Mar 2021
- Primary completionJan 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Orthostatic TremorStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- National Organization for Rare Disorders
- Responsible party
- Principal investigator, Robert Chen, University Health Network, Toronto
- Investigators
- Robert Chen, MBBS, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05547620
- Sponsor's protocol ID
- 20-5740
- Acronym
- LIFUS-POT
- Status last verified
- Feb 2026
- First submitted
- 3 Mar 2022
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulating Dysfunctional Cerebellar Activity With Low-intensity Focused Ultrasound Stimulation for Primary Orthostatic Tremor
- ClinicalTrials.gov ID
- NCT05547620
- Acronym / sponsor ID
- LIFUS-POT / 20-5740
- Conditions
- Orthostatic Tremor
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- National Organization for Rare Disorders
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 21 Sep 2022 (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.
Primary orthostatic tremor (POT) is a rare movement disorder that is manifested through high frequency tremor of weight bearing limbs. This is often accompanied by a debilitating sensation of falling. POT has been linked to abnormal activity of the cerebellum, a structure deep within the brain. However, established non-invasive brain stimulation techniques can only modulate brain activity and plasticity in superficial brain areas with low spatial resolution. This limits their efficacy when targeting the cerebellum. In contrast, low intensity focused ultrasound (LIFUS) is a novel non-invasive brain stimulation technique that permits stimulation with high spatial focality and can reach greater depth compared other methods. Therefore, LIFUS is well suited to modulate cerebellar activity and has the potential to be a superior technique for the management of POT. This study will investigate the effectiveness of MRI-guided bilateral cerebellar LIFUS stimulation for the treatment of POT and evaluate the underlying changes in brain circuits caused by the stimulation. Comparisons between symptoms and connectivity of brain circuits pre- and post-stimulation will be conducted to assess the effects of cerebellar LIFUS. The effects of real stimulation will also be compared to sham stimulation. This study is the first to apply LIFUS for neuromodulation in POT and will be critical in developing therapeutic LIFUS protocols.
Detailed description
In the current study the investigators aim to assess the effects of low intensity focused ultrasound (LIFUS) on the symptoms of primary orthostatic tremor (POT) and on brain connectivity. LIFUS is a promising non-invasive brain stimulation technique that is actively being studied for its ability to reversibly modulate brain activity. By focusing the propagation of acoustic wave through the skull, a higher degree of spatial specificity and deep targeting can be achieved over other non-invasive stimulation methods such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). Specifically, investigators will use LIFUS to stimulate the cerebellum bilaterally for 80s per hemisphere using a theta burst protocol that investigators have shown to induce plasticity. Investigators hypothesize that modulating cerebellar activity will decrease symptoms of POT and normalize the dysfunctional cerebello-thalamo-cortico network. 15 POT patients will be recruited to participate in 3 sessions in-lab. The first visit will involve an anatomical magnetic resonance image (MRI) scan. This will allow us to accurately target cerebellar lobule VIII and establish the appropriate parameters of LIFUS to effectively pass through the skull. In visits 2 and 3 participants will be seated in a comfortable chair and an anatomical MRI image will be used to position the LIFUS transducer over cerebellar lobule VIII bilaterally on surface of their head. In visit 2, clinical assessments of POT will be conducted through electromyography (EMG) recordings and video analysis of posture and sway. Symptoms prior to and after LIFUS will be compared. Investigators will compare the effects of real stimulation to a sham stimulation. In visit 3, Investigators will assess brain network activity using transcranial magnetic stimulation (TMS) by employing an established paired-pulse paradigm. This method will allow us to establish the effects of LIFUS on the cerebello-thalamo-cortical network and determine how this related to changes observed in POT symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Low Intensity Focused ultrasound | Experimental | Device: LIFUS Online Real, Device: LIFUS Online Sham, Device: LIFUS OfflineNeuroFUS device stimulation with 4 channel transducer Stimulation target = Cerebellum |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18-90 years of age
- Confirmed diagnosis of orthostatic tremor
Key exclusion criteria (12 listed)
- History of stroke or seizure
- Comorbid dementia
- Scored below 22 on the Montreal Cognitive Assessment (MoCA)
- Has intracranial implant(s) or device(s)
- Has an implanted cardiac pacemaker or implantable cardioverter-defibrillator (ICD)
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 |
|---|---|---|
| LIFUS Online RealStimulation using NeuroFUS device while standing | Device | Low Intensity Focused ultrasound |
| LIFUS Online ShamStimulation using NeuroFUS device while standing | Device | Low Intensity Focused ultrasound |
| LIFUS OfflineStimulation using NeuroFUS device prior to standing | Device | Low Intensity Focused ultrasound |
Primary outcome
Tremor frequency
Time frame: 2 Years
The primary outcomes will consist of peak tremor frequency recorded from surface electromyography (EMG). The EMG electrodes will be placed on the skin, and electrical activity produced by muscle contractions will be recorded. From the recordings of EMGs, peak frequency will be extracted through statistical analyses.
Power spectral analysis
Time frame: 2 Years
Power spectrum recorded from surface electromyography (EMG). The EMG electrodes will be placed on the skin, and electrical activity produced by muscle contractions will be recorded. From the recordings of EMGs, power spectrum will be extracted through statistical analyses.
Orthostatic Tremor Severity and Disability Scale (OT-10)
Time frame: 2 Years
The Orthostatic Tremor Severity and Disability Scale (OT-10) is a self-administered 10-item scale that measures the severity and disability of orthostatic tremor. Each item is rated from 0-5, with higher scores representing worse outcome.
2 secondary outcomes
Assessment of body posture
Time frame: 2 Years
Standing time
Time frame: 2 Years
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 24 Feb 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Robert Chen, MBBS principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LIFUS Online Real and LIFUS Offline in people with Orthostatic Tremor, run by University Health Network, Toronto at 1 site in Canada.
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 12 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: under way, not looking for participants, as of the sponsor's last update on 24 Feb 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tremor frequency (time frame: 2 Years). The study lists 3 primary outcomes in all. 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 24 Feb 2026; AzTrials last refreshed its copy on 26 Oct 2026.