Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy

Cerebellar Transcranial Magnetic Stimulation for Motor Control in Progressive Supranuclear Palsy

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.

Study Overview

• Status: Recruiting
• Conditions: Supranuclear Palsy, Progressive; Palsy Supranuclear
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation (rTMS)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Graham Harker; Phone Number: 5034182601; Email: balance@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Graham Harker; Phone Number: 5034182601; Email: balance@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active TMS first; 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); 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.
Experimental: Sham treatment first; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); Department of Health and Human Services; National Center for Advancing Translational Sciences (NCATS); Collins Medical Trust; National Center of Neuromodulation for Rehabilitation
• Investigators: Principal Investigator: Marian L Dale, MD, MCR, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Estimated): January 6, 2027
• Study Completion (Estimated): April 20, 2027

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: repetitive transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Supranuclear Palsy, Progressive
• Other Study ID Numbers: STUDY0020341; P2CHD086844 (U.S. NIH Grant/Contract); KL2TR002370 (U.S. NIH Grant/Contract); K23NS121402 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No