rTMS Therapy for Primary Orthostatic Tremor

March 14, 2025 updated by: University of Florida

rTMS Therapy for Primary Orthostatic Tremor: A Novel Treatment Approach

Primary orthostatic tremor(POT) is a rare progressive functionally disabling tremor disorder. The characteristic features of POT are symptoms of unsteadiness in legs reported by patients when they are standing and improvement of symptoms upon walking and sitting. Due to the limited success of other treatment options there is a clear merit in continuing efforts to explore and investigate novel treatment modalities. Transcranial magnetic stimulation (TMS) is a well-established physiological tool to understand brain function. When repetitious TMS pulses are delivered to a specific target at predefined stimulation parameters, it is referred to as rTMS therapy.The investigators propose a novel approach to investigate the clinical and physiological effects of low frequency rTMS therapy in POT. The overarching hypothesis of this study is that low frequency rTMS therapy delivered to the cerebellum will modulate the cerebellar excitability and result in clinical improvements.In order to determine the physiological effects related to rTMS, the tremor physiology will also be recorded with surface electromyography (EMG). The investigator will also record the changes in cerebellum excitability in response to rTMS using cerebello-cortical inhibition (CBI), a well-established TMS parameter.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

POT tremors recorded on surface electromyography (EMG) reveal distinct high frequency bursts of 13-18 Hz tremors in the leg muscles. POT was first described in 1984 at the University of Florida. Since then several clinical descriptions have been published however despite this knowledge for thirty years, treatment opportunities for POT have remained poor. Several medications have been tried, but the results have been disappointing. Thalamic deep brain stimulation (DBS) surgery, which is an invasive therapy approved by the FDA for treatment of essential tremor, was recently investigated in POT but the early results have only been partially successful. In clinical descriptions, POT has been observed to be associated with clinical features of cerebellar dysfunction such as dysmetria and gait ataxia. Positron emission tomography (PET) imaging has shown an increased activation of bilateral cerebellum related either to a mismatch between the peripheral afferent and the cerebellar efferent traffic or to a primary disorder of the cerebellum. MRI study has confirmed a cerebellar atrophy in POT and finally transcranial magnetic stimulation (TMS), has shown POT can be reset by stimulation of the cerebellum. The primary goal of this study is to test the efficacy of low frequency rTMS therapy in POT. The first aim of the study is to determine the clinical impact of 1-Hz rTMS therapy in POT when delivered to the cerebellum. This impact will be evaluated by the clinical scoring of leg tremors in standing posture, and the functional assessment of gait mobility. The second aim of this study is to determine the physiological effects of 1-Hz rTMS therapy in POT when delivered to the cerebellum. The investigator will determine the effects on the amplitude and frequency of tremors recorded with surface EMG. They will also determine the effects on the cerebello-cortical inhibition measured with TMS. Comparisons will be drawn between before rTMS therapy, immediately or +5 minutes after and 60+ minutes after assessments to determine the time course of effects. In this application, subjects with POT will be enrolled based on clinical history, physical exam and a 13-18 Hz tremor recorded on the surface EMG in accordance with the Consensus Statement of the Movement Disorder Society. Data will be presented as mean (SD) unless otherwise indicated. For each of the outcome variables, the statistical analyst will conduct a mixed model analysis using time and stimulation arm as repeated factors adjusted for baseline values, and subjects as the random factor.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32607
        • Center for Movement Disorders and Neurorestoration

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Potential participants will be diagnosed with Primary orthostatic tremor (POT) and be recruited through IRB approved database maintained by the Movement Disorders Center

Exclusion Criteria:

  • Pregnancy
  • Active seizure disorder
  • Significant cognitive impairment
  • Presence of a metallic body such as pacemaker, implants, prosthesis,artificial limb or joint, shunt, metal rods and hearing aid

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Real rTMS Stimulation
rTMS will be delivered over each cerebellar hemisphere, using a 70mm figure-of-eight coil connected to a Magstim RapidStim2 machine while positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. The inion will be taken as the boundary between the posterior cerebellum and the occipital cortex. Therefore the area stimulated will be caudal to the inion to stimulate the posterior cerebellum.
Device: Magstim RapidStim2
Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.
Other: Timed "Up & Go" Test (TUG) test
All participants will receive a clinical assessment of basic mobility skills by using the TUG test.
Other: 10m walk test
All participants will receive a clinical assessment of walking speed by using the walk test.
Other: Tremor electrophysiology
All participant tremors will by analyzed using an EMG system
Other: Fullerton Advanced Balance (FAB) Scale
All participants will receive a clinical assessment of balance ability and fall risk.
Other: Cerebellar-brain Inhibition (CBI)
All participants will have a measure of the cerebellar-brain inhibition (CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Sham Comparator: Sham rTMS Stimulation
Patients randomized to receive sham treatment will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham Magstim RapidStim2 Placebo which produces discharge noise and vibration similar to the real coil without stimulating the cerebral cortex. However, in addition to obvious coil discharge noise, rTMS also causes electrical stimulation of the scalp. The investigator will simulate this experience by attaching surface electrodes underneath the sham coil and in contact with the scalp. The investigator will use an electromyography to administer electrical shocks to the scalp simultaneous to each simulated rTMS train.
Other: Timed "Up & Go" Test (TUG) test
All participants will receive a clinical assessment of basic mobility skills by using the TUG test.
Other: 10m walk test
All participants will receive a clinical assessment of walking speed by using the walk test.
Other: Tremor electrophysiology
All participant tremors will by analyzed using an EMG system
Device: Sham Magstim RapidStim2
Same procedure as real rTMS without stimulating the cerebral cortex.
Other: Fullerton Advanced Balance (FAB) Scale
All participants will receive a clinical assessment of balance ability and fall risk.
Other: Cerebellar-brain Inhibition (CBI)
All participants will have a measure of the cerebellar-brain inhibition (CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Fullerton Advanced Balance (FAB) Scale Total Score After rTMS
Time Frame: Pre- to Post-Intervention, on average 3 hours
The Fullerton Advanced Balance (FAB) Scale is a clinical assessment of balance ability and fall risk. Participants complete 10 physical activity challenges while observed, and their performance is rated on a 0-4 scale, where a higher score a greater ability to balance. Each item is then summed to generate a Total Score, ranging from 0-40, where a higher total score indicates greater overall balance and lower likelihood of fall risk. The reported measure is the change in the FAB Total Score from before and after, where a positive value implies improvement in balance, a negative value indicates a worsening of balance, and 0 indicates no change.
Pre- to Post-Intervention, on average 3 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tremor electrophysiology
Time Frame: Day 1
POT tremors will be recorded on the surface EMG for amplitude and power spectral frequency analysis. The investigator will use Bagnoli EMG system and Trigno wireless EMG system to record the surface EMG signals arising from muscles and the accelerometer findings respectively.Tremor amplitude and frequencies will be calculated with the surface EMG using Bagnoli system and accelerometry recorded using Trigno system.
Day 1
TMS measure
Time Frame: Baseline to 60 Minutes
Cerebellar inhibition (CBI) will be recorded which is a well-established TMS measure. A paired pulse protocol will be used with right cerebellar stimulation as the conditioning stimulus, (cerebellar conditioning stimulus or CCS) and left motor cortex stimulation (M1) as the test stimulus (TS). The investigator will determine the 'TS 0.5mV' which will indicate a stimulator setting (determined to the nearest 1% of the maximum stimulator output) that produces a peak-to-peak MEP amplitude of ≥0.5mV in at least five out of 10 trials. Interstimulus intervals (ISI) of 3 to 8 milliseconds at increment of 1 millisecond will be tested. Each run will consist of 10 trials of each of the paired stimuli (CCS-TS) and 10 trials of TS alone delivered in random order. Inhibition trial will be expressed as a ratio of mean conditioned to mean unconditioned MEP amplitude for each subject.
Baseline to 60 Minutes

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Standing Duration
Time Frame: Pre- to Post-Intervention, on average 3 hours apart
Participants were asked to stand for as long as they could. Their standing duration was video recorded and timed in seconds. The measure reported is the change in standing time from before to after the rTMS intervention, where a positive value indicates an improvement in standing duration, a negative value indicates a worsening of standing duration, and 0 indicates no change.
Pre- to Post-Intervention, on average 3 hours apart
Timed "Up & Go" Test (TUG) Test
Time Frame: Pre- to Post-Intervention
The TUG is a mobility test that is used to measure the basic mobility skills and gait speed of people who have neurological conditions. It includes a sit-to-stand component as well as walking 3 m, turning, and returning to the chair. People perform these tasks using regular footwear and customary walking aids. The measured outcome is the time in seconds to complete the entire sequence. For the outcome assessment the test will be videotaped and scored by a blind rater. We calculated the change between two time points (pre intervention value minus post intervention value)
Pre- to Post-Intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Neuronetics
National Organization for Rare Disorders

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Aparna Wagle-Shukla, M.D., Center for Movement Disorders and Neurorestoration

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 8, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 8, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 2, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201500347

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Primary Orthostatic Tremor

Clinical Trials on Magstim RapidStim2

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings