Repetitive Transcranial Magnetic Stimulation (TMS) for Progressive Supranuclear Palsy and Corticobasal Degeneration

May 7, 2014 updated by: Choi Deblieck, University of California, Los Angeles

Noninvasive Cortical Stimulation (rTMS) for Motor and Non-Motor Features of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD)

Drug therapy of atypical parkinsonism is generally considered either ineffective or minimal 1. Therefore, there is an urgent need to find alternative therapies to treat atypical parkinsonian disorders. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool that modulates cortical excitability with minimal discomfort and holds therapeutic promise in treating neurological and psychiatric disorders.

The basal ganglia-thalamocortical circuits that are affected in Progressive Supranuclear Palsy (PSP) and Corticocbasal Ganglionic Degeneration (CBGD) are likely structurally and functionally segregated. The 'motor' circuit is implicated in parkinsonian akinesia and hypokinesia; a 'prefrontal' circuit is implicated in working memory and mood regulation, and linked with non-motor symptoms such as depression and apathy. In this proposal, we characterize motor and prefrontal network dysfunction in PSP and CBGD patients, and propose that high-frequency and low-frequency rTMS directed over separate motor and prefrontal cortical targets of each network may show specific and selective beneficial effects on motor vs. cognitive function in PSP and CBGD patients, respectively. Quantitative motor outcome measures include timed finger tapping tasks. Quantitative cognitive outcome measures comprise a visual analogue scale (VAS).

If successful, this pilot study will provide proof of principle data to suggest potential benefits for rTMS in PSP/CBGD patients, and provide sufficient data and experience to support future PSP/CBGD studies that include the use of rTMS to investigate the pathophysiology of motor and non-motor features of PSP and CBGD patients.

Study Overview

Status

Completed

Conditions

Detailed Description

Background: Drug therapy of atypical parkinsonism is generally ineffective or minimal, and novel therapy approaches for atypical parkinsonian disorders are needed. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool that modulates cortical excitability and holds promise in treating neurological/psychiatric disorders. The 'motor' basal ganglia-cortical circuit is implicated in parkinsonian akinesia and hypokinesia; a 'prefrontal' circuit is implicated in working memory (WM) and mood regulation, possibly linked to depression and apathy.

Hypothesis: Motor deficits in Progressive Supranuclear Palsy (PSP) and Corticobasal Ganglionic Degeneration (CBGD) are associated with a dysfunctional motor network; emotional deficits in PSP/CBGD are associated with a dysfunctional prefrontal network. We hypothesize that high-frequency and low-frequency rTMS over cortical targets will selectively and specifically improve tasks and symptoms relevant to that target in PSP and CBGD patients, respectively.

Aims: To contrast cortical excitability characteristics and motor and emotional function between PSP and CBGD patients. To determine selective and specific beneficial rTMS effects over primary motor (M1) and dorsolateral prefrontal (DLPFC) cortex on cortical excitability characteristics and motor and emotional function in PSP and CBGD patients.

Design: Ten individuals with PSP and ten with CBGD will participate in a within-subject cross-sectional design. Motor outcome measures include a timed finger tapping task at comfortable and maximal speed. Quantitative cognitive outcome measures comprise a visual analogue scale of mood states (VAS). After a first baseline visit, PSP patients will receive high-frequency 5 Hz rTMS in two separate visits to two site conditions (left DLPFC vs. the more affected side of M1) across subjects with two within-session task conditions (motor vs. cognitive). They will also receive sham stimulation in a separate visit. These three stimulation visits will be randomized. CBGD patients will receive the same treatment with the only difference that they will receive low-frequency 1 Hz rTMS instead.

Relevance: If successful, we will demonstrate a double-dissociation and causal functional significance between rTMS modulation of M1 in motor tasks and DLPFC in emotional function in PSP Vs. CBGD. Exploratory aims will be conducted. Sufficient data and experience for future PSP/CBGD intervention studies will help identify candidate TMS parameters that are optimal for given symptoms.

Study Type

Observational

Enrollment (Actual)

30

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
    • California
      • Los Angeles, California, United States, 90095
        • UCLA

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

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The purpose of this study is to learn more about how transcranial magnetic stimulation (TMS) affects motor and non-motor function in patients with Progressive Supranuclear Palsy (PSP) or Cortical Basal Ganglionic Degeneration (CBGD)-forms of parkinsonism.

Description

Inclusion Criteria:

If you are an adult with PSP or CBGD:

1. Must be in good physical health.

If you are neurologically healthy volunteers:

1. Must be older than 35 years

Exclusion Criteria:

  1. Must have no implanted metal. Dental fillings are acceptable.
  2. Must have no personal seizure or 1st degree relative with history of seizures
  3. Must not take any medication that lowers seizure threshold.

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

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
PSP patients
People that have been clinically diagnosed with atypical parkinsonism, i.e., PSP
CBD patients
People that have been clinically diagnosed with atypical parkinsonism, i.e., CBD
Age-matched healthy controls
People that have not been diagnosed with any kind of neurologic movement disorder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical excitability (CE) measures expressed in motor evoked potentials (MEP)
Time Frame: 1 hour
We assess cortical excitability (CE) with motor evoked potentials (MEP) and cortical silent periods (CSP) before and after repetitive Transcranial Magnetic Stimulation (TMS).
1 hour

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
visual analog scale (VAS)
Time Frame: 2 min
We assess mood with a visual analog scale (VAS) of 5 emotions and 1 overall feeling of well-being.
2 min
tapping speed
Time Frame: 5 min
tapping speed (movement time and reaction time) will be measured
5 min

Collaborators and Investigators

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

Sponsor

University of California, Los Angeles

Investigators

  • Principal Investigator: Allan Wu, M.D., UCLA Neurology

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

October 1, 2008

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

February 1, 2012

Study Registration Dates

First Submitted

July 28, 2010

First Submitted That Met QC Criteria

August 3, 2010

First Posted (Estimate)

August 4, 2010

Study Record Updates

Last Update Posted (Estimate)

May 8, 2014

Last Update Submitted That Met QC Criteria

May 7, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCaliforniaLA
  • CurePSP (Other Grant/Funding Number: CurePSP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

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