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

Progressive Supranuclear Palsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01174771
• Other study ID #: UCaliforniaLA
• Secondary ID: CurePSP
• Status: Completed
• Phase: N/A
• First received: July 28, 2010
• Last updated: May 7, 2014
• Start date: October 2008
• Est. completion date: February 2012

Study information

• Verified date: May 2014
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 35 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Corticobasal Degeneration
• Parkinsonian Disorders
• Parkinsonism
• Progressive Supranuclear Palsy
• Supranuclear Palsy, Progressive

Locations

Country	Name	City	State
United States	UCLA	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (14)

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Epstein CM, Evatt ML, Funk A, Girard-Siqueira L, Lupei N, Slaughter L, Athar S, Green J, McDonald W, DeLong MR. An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease. Clin Neurophysiol. 2007 Oct;118(10):2189-94. Epub 2007 Aug 21. — View Citation

Filipovic SR, Rothwell JC, van de Warrenburg BP, Bhatia K. Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease. Mov Disord. 2009 Jan 30;24(2):246-53. doi: 10.1002/mds.22348. — View Citation

Khedr EM, Farweez HM, Islam H. Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson's disease patients. Eur J Neurol. 2003 Sep;10(5):567-72. — View Citation

Lang P. The international affective picture system [photographic slides]. Technical report. Gainsville, FL: The Center for Research in Phycophysiology, University of Florida; 1988.

Lefaucheur JP, Drouot X, Von Raison F, Ménard-Lefaucheur I, Cesaro P, Nguyen JP. Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease. Clin Neurophysiol. 2004 Nov;115(11):2530-41. — View Citation

Lefaucheur JP, Fénelon G, Ménard-Lefaucheur I, Wendling S, Nguyen JP. Low-frequency repetitive TMS of premotor cortex can reduce painful axial spasms in generalized secondary dystonia: a pilot study of three patients. Neurophysiol Clin. 2004 Oct;34(3-4):141-5. — View Citation

Murase N, Rothwell JC, Kaji R, Urushihara R, Nakamura K, Murayama N, Igasaki T, Sakata-Igasaki M, Mima T, Ikeda A, Shibasaki H. Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp. Brain. 2005 Jan;128(Pt 1):104-15. Epub 2004 Oct 13. — View Citation

Pascual-Leone A, Rubio B, Pallardó F, Catalá MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. — View Citation

Rektorova I, Sedlackova S, Telecka S, Hlubocky A, Rektor I. Dorsolateral prefrontal cortex: a possible target for modulating dyskinesias in Parkinson's disease by repetitive transcranial magnetic stimulation. Int J Biomed Imaging. 2008;2008:372125. doi: 10.1155/2008/372125. — View Citation

Siebner HR, Mentschel C, Auer C, Conrad B. Repetitive transcranial magnetic stimulation has a beneficial effect on bradykinesia in Parkinson's disease. Neuroreport. 1999 Feb 25;10(3):589-94. — View Citation

Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B. Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson's disease. J Neurol Sci. 2000 Sep 15;178(2):91-4. — View Citation

Stern WM, Tormos JM, Press DZ, Pearlman C, Pascual-Leone A. Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial. J Neuropsychiatry Clin Neurosci. 2007 Spring;19(2):179-86. — View Citation

Tumas V, Rodrigues GG, Farias TL, Crippa JA. The accuracy of diagnosis of major depression in patients with Parkinson's disease: a comparative study among the UPDRS, the geriatric depression scale and the Beck depression inventory. Arq Neuropsiquiatr. 2008 Jun;66(2A):152-6. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortical excitability (CE) measures expressed in motor evoked potentials (MEP)	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	No
Secondary	visual analog scale (VAS)	We assess mood with a visual analog scale (VAS) of 5 emotions and 1 overall feeling of well-being.	2 min	No
Secondary	tapping speed	tapping speed (movement time and reaction time) will be measured	5 min	No