Cerebellar rTMS Theta Burst for Postural Instability in Progressive Supranuclear Palsy (CerTI-PSP)

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

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.

Study Overview

• Status: Completed
• Conditions: Fall; Parkinsonism; Progressive Supranuclear Palsy; Gait, Rigid
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Trescore Balneario, Italy
    • Parkinson's disease Rehabilitation Centre - FERB ONLUS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Real Stimulation; 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; Cerebellar repetitive theta Burst stimulation will be performed as detailed in the Real arm description; Other Names: rTMS; theta Burst, rTMS
SHAM_COMPARATOR: Sham Stimulation; 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; Cerebellar repetitive theta Burst stimulation will be performed as detailed in the Real arm description; Other Names: rTMS; theta Burst, rTMS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Europea di Ricerca Biomedica Ferb Onlus
• Collaborators: University of Brescia, Neurology Department; University of Kiel, Neurogeriatric Department
• Investigators: Principal Investigator: Andrea Pilotto, MD, Università degli Studi di Brescia

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2017
• Primary Completion (ACTUAL): November 1, 2019
• Study Completion (ACTUAL): November 15, 2019

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (ACTUAL): January 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 18, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: cerebellum; repetitive Transcranial Magnetic stimulation; wearing sensors; static balance
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Paralysis; Ophthalmoplegia; Parkinsonian Disorders; Supranuclear Palsy, Progressive; Gait Disorders, Neurologic
• Other Study ID Numbers: 191201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The whole project will be published in medical journal
• IPD Sharing Time Frame: In the publication, within the next year
• IPD Sharing Access Criteria: on-line availability
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No