Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy

Study Overview
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Brief Summary
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The objective of this proposal is to investigate the effect of non-invasive repetitive cerebellar transcranial magnetic stimulation (rTMS) on motor control in progressive supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via cerebellar rTMS will decrease postural instability in patients with PSP. We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS.

Official Title
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Cerebellar Transcranial Magnetic Stimulation for Motor Control in Progressive Supranuclear Palsy

Conditions
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Palsy Supranuclear, Supranuclear Palsy, Progressive

Intervention / Treatment
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* Device: Repetitive transcranial magnetic stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: probable or possible PSP by the revised MDS PSP Criteria (Hoglinger 2017) age 40-85 at time of screening ability to understand and cooperate with simple instructions in English ability to read at 6th grade reading level in English ability to stand unassisted for at least 30 seconds and to be able walk independently with a walker ability to refrain from new physical and speech therapy programs for the duration of the study ability to remain on stable doses of any cholinergic, dopaminergic, serotonergic sedative or NMDA receptor antagonists for the duration of the study females of child-bearing age must perform a urine pregnancy test and be on reliable birth control during the course of the study Exclusion Criteria: other significant neurological or vestibular disorders presence of electrically, magnetically or mechanically activated implants or history of injurious metal exposure in eyes, head, or body

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The investigators will use a single-blind crossover design with a 4 week TMS washout period. The subjects will serve as their own controls, thus limiting confounding variables such as medication or cognitive effect.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active TMS first<br>After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week TMS intervention. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week sham TMS period prior to their final assessment. | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Aim 1: To determine the clinical effects of rTMS targeting the cerebellum on postural instability in PSP. The hypothesis to be tested is that TMS augmentation of cerebellar inhibition will improve cerebellum-dependent balance symptoms of PSP for a period of time sufficient to improve rehabilitation outcomes. The investigators will measure a battery of objective posturography metrics and other measures of motor control, including sway and center of pressure changes to backward tilt and forward translation. Aim 2: We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS. The hypothesis to be tested is that premotor and motor cortical activity will decrease after cerebellar rTMS compared to sham TMS, reflecting improved cerebellar inhibition of the motor cortex after the intervention.<br>|
| Experimental: Sham treatment first<br>After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week sham TMS period. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week TMS intervention prior to their final assessment. | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Aim 1: To determine the clinical effects of rTMS targeting the cerebellum on postural instability in PSP. The hypothesis to be tested is that TMS augmentation of cerebellar inhibition will improve cerebellum-dependent balance symptoms of PSP for a period of time sufficient to improve rehabilitation outcomes. The investigators will measure a battery of objective posturography metrics and other measures of motor control, including sway and center of pressure changes to backward tilt and forward translation. Aim 2: We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS. The hypothesis to be tested is that premotor and motor cortical activity will decrease after cerebellar rTMS compared to sham TMS, reflecting improved cerebellar inhibition of the motor cortex after the intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective posturography | The primary endpoint is center of pressure shifts with tilt and with translation, and body sway in quiet stance. | assessed on 4 days during the 8 week study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fNIRS | functional near infrared spectroscopy of premotor and motor areas during balance testing | assessed on 4 days during the 8 week study period | 
| speech analysis | speech sample assessment conducted by investigator | assessed on 4 days during the 8 week study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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repetitive transcranial magnetic stimulation