Cerebellar rTMS Theta Burst for Postural Instability in Progressive Supranuclear Palsy

Study Overview
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Brief Summary
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Objective of the study: To test the efficacy of theta burst cerebellar stimulation on postural instability in progressive supranuclear palsy using a cross-over design and wearing sensors technology Design: Twenty probable PSP patients with no dementia and still able to walk will be recruited for a cross-over sham-controlled study. Each patient will undergo a sham stimulation or a single session of cerebellar theta burst stimulation with a wash out period of at least 14 days. Each patient will be evaluated before and after stimulation by berg balance tests (BBS), Tinetti scale, PSP-rating scale (PSP-RS), and a battery of gait and movement tests. Static balance was assessed by 30-seconds-trials in semitandem and tandem positions with eyes open and closed using wearing sensors technology.

Detailed Description
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Background: There are no medical effective treatments for progressive supranuclear palsy (PSP). Imaging, neurophysiology and pathology studies suggested cerebellum as possible target of brain stimulation for postural instability using theta Burst repetitive Transcranial magnetic stimulation Objective of the study: To test the efficacy of theta burst cerebellar stimulation on postural instability in progressive supranuclear palsy using a cross-over design and wearing sensors technology Design: Probable PSP patients able to walk and without dementia/behavioral disturbances will be recruited for a cross-over sham-controlled study. Each patient will undergo a sham stimulation or a single session of cerebellar theta burst stimulation with a wash out period of at least 14 days. Repetitive cerebellar theta burst stimulation will be performed by Duo-Mag XT100, using a 3 pulses at 50-Hz repeated at a rate of 5-Hz; 20 trains of 10 bursts given with 8-s intervals for a total of 600 pulses. Intensity of rTMS was set at the 80% of Amplitude of Motor Threshold (RMT) obtained in the left motor cortex for each subject. A sample size of 20 subjects with complete stimulation (2 stimulations per subject, for a total number of stimulation) Each patient will be evaluated before and after stimulation by berg balance tests (BBS), Tinetti scale, PSP-rating scale (PSP-RS), and a battery of gait and movement tests. Static balance was assessed by 30-seconds-trials in semitandem and tandem positions with eyes open and closed using wearing sensors technology. Sensors assessment: The following parameters will be evaluated before and after stimulation (real vs sham): The parameter i) TIME, defined as time without falling ii) The parameter surface, defined as the sway area iii) Velocity describes the mean velocity of the compensatory movements given in mm/s. iv) Acceleration described as root mean square (RMS), v) Jerk, the time derivate of acceleration, quantifies smoothness of the compensatory movements given in mG/s.

Official Title
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Cerebellar rTMS Theta Burst for Postural Instability in Progressive Supranuclear Palsy: a Double Blind Cross-over Sham-controlled Study Using Wearing Sensors Technology

Conditions
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Progressive Supranuclear Palsy, Fall, Gait, Rigid, Parkinsonism

Intervention / Treatment
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* Device: repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: probable PSP diagnosis ability to stand alone without support for at least 5 seconds ability to walk without aid for at least three meters Exclusion Criteria: dementia or behavioral alterations contraindications of stimulation

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: Each patient received both rTMS and sham cerebellar stimulation in randomized order in two different sessions, separated by at least 2 weeks. In each session, motor tasks, clinical scales and wearing sensor assessments were tested twice in all patients: at baseline (pre-stimulation) and after rTMS (post-stimulation)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real Stimulation<br>Cerebellar Repetitive theta burst stimulation will be performed using a 3 pulses at 50-Hz repeated at a rate of 5-Hz; 20 trains of 10 bursts given with 8-s intervals for a total of 600 pulses. Intensity of rTMS was set at the 80% of Amplitude of Motor Threshold (RMT) obtained in the left motor cortex for each subject. | Device: repetitive transcranial magnetic stimulation<br>* Cerebellar repetitive theta Burst stimulation will be performed as detailed in the Real arm description<br>* Other names: theta Burst, rTMS;|
| Sham Comparator: Sham Stimulation<br>The rTMS coil stimulation will be applied in the same position of the real stimulation. The Stimulation will be performed like in the real arm with the difference that the coil will be masked and thus will be inactive. The patient will hear the same sound of real stimulation, which will be only functionally inactive but will be completely performed (for the whole time of duration of stimulation) | Device: repetitive transcranial magnetic stimulation<br>* Cerebellar repetitive theta Burst stimulation will be performed as detailed in the Real arm description<br>* Other names: theta Burst, rTMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Physical Performance Battery, total time (SPPB) | The short Physical performance battery included a walking test at convenient speed, a chair-rise test at convenient speed and tests of static balance including feet together, semi-tandem and tandem stance) | Changes from Baseline to immediately after stimulation | 
| Timed up and Go tests, total time (TUG) | The time of performance of two timed up and go test ( one starting with the right foot, one starting with the left foot) will be assessed | Changes from Baseline to immediately after stimulation | 
| Static Balance tests, total time | The assessment of static balance will include four tasks, in which the patient has to stand alone and maintain the position in different conditions for up to 30 seconds: tandem and semitandem positions with eyes closed and eyes open, respectively. The time of performance without falling will be assessed. | Changes from Baseline to immediately after stimulation | 
| Tinetti Balance test (TBT) | Assessment of postural instability (0-28, higher scores indicate better performances) | Changes from Baseline to immediately after stimulation | 
| Static Balance- area of sway | The area of sway during the postural instability tasks will be assessed (unit of measure mm2) | Changes from Baseline to immediately after stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSP rating scale (PSP-RS) | Assessment of postural instability and disability of patients (scores ranging from 0 to 100, lower scores indicate less disability) | Changes from Baseline to immediately after stimulation | 
| Static Balance: wearable sensor analyses - velocity | the velocity of sway will be assessed during the postural instability tasks (unit of measure (mm/s) | Changes from Baseline to immediately after stimulation | 
| Static Balance: wearable sensor analyses - acceleration | the acceleration of sway will be assessed during the postural instability tasks (unit of measure mm2/s) | Changes from Baseline to immediately after stimulation | 
| Static Balance: wearable sensor analyses - jerk | The time-derived of acceleration of sway will be assessed during the postural instability tasks (unit of measure mm3/s) | Changes from Baseline to immediately after stimulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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repetitive Transcranial Magnetic stimulation, cerebellum, wearing sensors, static balance