LIFUS for Orthostatic Tremor

(LIFUS-POT Trial)

Overseen By Julian Kwok

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Antipsychotics, Marijuana, Recreational drugs

Disqualifiers: Stroke, Seizure, Dementia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called low intensity focused ultrasound (LIFUS) for individuals with primary orthostatic tremor (POT), a rare condition that causes shaky legs when standing and a fear of falling. LIFUS is a non-invasive brain stimulation method that targets the cerebellum, a part of the brain linked to POT, and may improve symptoms more effectively than current techniques. The trial will compare the effects of real and sham LIFUS to observe any changes in brain activity and tremor symptoms. Individuals with a confirmed diagnosis of orthostatic tremor might be suitable candidates for this study. As an unphased trial, this study provides a unique opportunity to explore a novel treatment approach for POT.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on antipsychotics, marijuana, or other recreational drugs that affect the nervous system.

What prior data suggests that this LIFUS technique is safe for treating orthostatic tremor?

Research has shown that low-intensity focused ultrasound (LIFUS) is generally safe for people. One study examined LIFUS for treating movement disorders and chronic pain, finding it could safely stimulate the brain without serious side effects. Another study confirmed LIFUS's safe use in a clinical setting on the brain.

These findings suggest LIFUS is a promising and safe treatment option for those considering clinical trials. While new treatments always carry some risk, current evidence supports its safety for use in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the LIFUS treatment for Orthostatic Tremor because it uses Low Intensity Focused Ultrasound (LIFUS) to target the cerebellum, a part of the brain that plays a key role in motor control. Unlike current treatments that primarily rely on medications like beta-blockers or benzodiazepines, which can have significant side effects, LIFUS offers a non-invasive approach. This method aims to modulate brain activity directly without the need for drugs, potentially offering a safer and more precise alternative.

What evidence suggests that LIFUS is effective for orthostatic tremor?

Research has shown that LIFUS (Low Intensity Focused Ultrasound) might help treat primary orthostatic tremor (POT) by targeting the cerebellum, a brain area linked to this condition. LIFUS offers precision and can reach deeper brain areas more effectively than other non-invasive methods. This trial will evaluate different versions of LIFUS, including LIFUS Online Real and LIFUS Online Sham, to assess their effectiveness in managing POT. Studies on similar movement disorders have found that LIFUS can alter brain activity and help reduce symptoms. For instance, it has been used successfully to treat essential tremor, another movement disorder, by lessening tremors through targeted brain stimulation. These encouraging results suggest that LIFUS could be a helpful option for managing POT. ^{1 2 3 4 6}

Who Is on the Research Team?

Robert Chen, MBBS

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-90 with a confirmed diagnosis of orthostatic tremor. It's not suitable for those with brain implants, previous movement disorder surgeries, pregnant women, severe depression or psychiatric disorders, cognitive impairment (MoCA score <22), pacemakers/ICDs, metal in the body contraindicated by MRI/TMS, drug use affecting the nervous system, major hand/wrist/limb diseases or systemic illness/infection.

Inclusion Criteria

I have been diagnosed with orthostatic tremor.

Exclusion Criteria

I have had a stroke or seizure in the past.

I am currently using antipsychotics, marijuana, or other recreational drugs.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI-guided bilateral cerebellar LIFUS stimulation to assess its effects on POT symptoms and brain connectivity

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• LIFUS Offline
• LIFUS Online Real
• LIFUS Online Sham

Trial Overview The study tests low intensity focused ultrasound (LIFUS) to modulate cerebellar activity in patients with primary orthostatic tremor. Participants will receive either real LIFUS stimulation while connected to an MRI machine or sham (fake) treatment to compare effects on their condition and brain circuitry changes.

How Is the Trial Designed?

Group I: Low Intensity Focused ultrasound Experimental Treatment 3 Interventions

NeuroFUS device stimulation with 4 channel transducer Stimulation target = Cerebellum

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

National Organization for Rare Disorders

Collaborator

Trials

5

Recruited

10,600+

Citations

1. withpower.com withpower.com/trial/phase-tremor-2-2021-467bd

LIFUS for Orthostatic Tremor (LIFUS-POT Trial) Trial Overview The study tests low intensity focused ultrasound (LIFUS) to modulate cerebellar activity in patients with primary orthostatic tremor.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12209223/

Low-intensity focused ultrasound of the spine in the treatment ... In this work, we review current advances in LIFU of the spine region for the treatment of chronic neuropathic pain and movement disorders.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5425801/

Focused Ultrasound for Essential Tremor: Review of the ... The purpose of this review is to discuss the new developments and trials of MRgFUS in the treatment of ET and other tremor disorders. Results.

4. clinicaltrial.be clinicaltrial.be/en/details/23033?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Modulating Cerebellar Activity With Low-intensity Focused... The primary outcomes will consist of peak tremor frequency recorded from surface electromyography (EMG). The EMG electrodes will be placed on ...

5. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2821255

Safety and Efficacy of Staged, Bilateral Focused ... In this open-label trial, 51 patients with essential tremor treated successfully unilaterally underwent focused ultrasound thalamotomy on the opposite side.

6. mdpi.com mdpi.com/2076-3417/15/9/4743

Focused Ultrasounds in the Rehabilitation Setting Huang et al. conducted a phase I trial demonstrating the safety and feasibility of low-intensity focused ultrasound (LIFUS) applied to the ipsilesional motor ...