Modulating Cerebellar Activity With Low-intensity Focused Ultrasound Stimulation for Primary Orthostatic Tremor

NCT05547620 | Active Not Recruiting

• 1 other identifier: 20-5740
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Orthostatic Tremor

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  2 Years

Secondary Outcomes (2)

• Assessment of body posture

  2 Years

• Standing time

  2 Years

Study Arms (1)

Low Intensity Focused ultrasound

EXPERIMENTAL

NeuroFUS device stimulation with 4 channel transducer Stimulation target = Cerebellum

Device: LIFUS Online Real; Device: LIFUS Online Sham; Device: LIFUS Offline

Interventions

LIFUS Online Real DEVICE

Stimulation using NeuroFUS device while standing

Low Intensity Focused ultrasound

LIFUS Online Sham DEVICE

Stimulation using NeuroFUS device while standing

Low Intensity Focused ultrasound

LIFUS Offline DEVICE

Stimulation using NeuroFUS device prior to standing

Low Intensity Focused ultrasound

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Confirmed diagnosis of orthostatic tremor

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• National Organization for Rare Disorders: collaborator

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Study Officials

• Robert Chen, MBBS

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: September 21, 2022
• Study Start: March 8, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)