Transcranial Magnetic Stimulation to Improve Speech in Aphasia

NCT ID: NCT00608582

Last Updated: 2017-01-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-07-31

Study Completion Date

2013-06-30

Brief Summary

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The purpose of this study is to examine whether repetitive transcranial magnetic stimulation (rTMS) can be used to improve speech in chronic stroke patients with aphasia. Aphasia patients can have problems with speech production. The rTMS procedure allows painless, noninvasive stimulation of human cortex from outside the head.

Chronic aphasia patients have been observed in our functional magnetic resonance brain imaging studies to have excess brain activation in brain areas possibly related to language on the right side of the brain (opposite side to where the stroke took place). It is expected that suppression of activity in the directly targeted brain region will have an overall modulating effect on the neural network for naming (and propositional speech) and will result in behavioral improvement.

Detailed Description

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OBJECTIVE: The purpose of this research is to investigate whether repetitive transcranial magnetic stimulation (rTMS) can improve speech in chronic stroke patients with aphasia. TMS allows painless, noninvasive stimulation of brain cortex (1 cm x 1 cm). Slow (1 Hz) rTMS appears to decrease excitability in the targeted cortical region of interest (ROI) leading to measurable behavioral effects. Chronic aphasia patients have been observed in our fMRI work (and others) to have increased activation in right (R) Broca's and other R language homologues during language tasks. It is hypothesized that suppression of activity in a directly targeted right hemisphere (RH) ROI will have an overall modulating effect on functionally connected elements of the distributed neural network for naming (and propositional speech), and will result in behavioral improvement.

RESEARCH PLAN AND METHODS:

Nonfluent aphasia patients (\>6 Mo. poststroke) will be studied. The rTMS treatments in Boston take place at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School under the supervision of Alvaro Pascual-Leone, M.D., Ph.D. and additional patients will be studied at the Hospital of the University of Pennsylvania, H. Branch Coslett, M.D., who is a P.I. on that subcontract. This is a blinded, randomized, sham-control, incomplete crossover design. Naming and language tests are obtained pre- and post- rTMS.

Treatment Design: Multiple Baseline Language Evaluations (x3) are performed at Entry (Boston Naming Test, BNT; and Boston Diagnostic Aphasia Exam, BDAE). Primary Outcome Measures are BNT; and Number of Words per Longest Phrase Length (cookie theft picture description) from the BDAE. Patients are randomly assigned to receive a series of either Sham rTMS followed by a series of Real rTMS; OR they receive only the series of Real rTMS. The Sham series is identical to the Real, however, no magnetic pulse is emitted from the coil, although the patient hears the same clicking sound emitted from the coil. Due to space limitation here, only the Real rTMS treatment schedule is described.

There are two rTMS Phases: During Phase 1, the single, best RH cortical ROI to suppress with rTMS to improve picture naming, is determined for each patient. Real rTMS (1 Hz, 90% motor threshold) is applied for 10 minutes, in separate rTMS sessions, to each of 4 different RH cortical ROIs (R ant. BA 45; R post. BA 45; R BA 44 and R M1, mouth). Snodgrass \& Vanderwart (S\&V, 1980) Picture Naming is tested immediately before and after each ROI has been suppressed with rTMS. The single RH ROI which is associated with at least a 2 SD improvement (above S\&V Naming, tested 3x at Baseline), immediately following 10 minutes of rTMS to suppress that cortical area, is considered to be the Best Response ROI for that patient. During Phase 2, the Best Response ROI from Phase 1 is suppressed for 20 minutes, 5 days per week, 2 weeks. All patients receive follow-up BNT and BDAE testing at 2 months following the 10th Real (or Sham) rTMS treatment.

Conditions

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Aphasia Cerebrovascular Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Real rTMS

These patients receive a series of 10 Real Transcranial Magnetic Stimulation, Repetitive (rTMS), treatments, only. There is pre-testing, and post-testing at 2 months after the last Real rTMS treatment.

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation, Repetitive

Intervention Type DEVICE

10 rTMS treatments (90% of motor threshold, 20 minutes, at 1 Hz) to specific right hemisphere area of brain cortex; 5 days per week for 2 weeks at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; or at the Neurology Department, Hospital of the University of Pennsylvania, Philadelphia, PA.

Sham rTMS

Patients receive a series of 10 Sham Transcranial Magnetic Stimulation, Repetitive (rTMS) treatments, followed by a series of 10 Real rTMS treatments. Sham rTMS treatments are identical to the Real rTMS treatments, however, no magnetic pulse is released. There is pre-testing, and post-testing at 2 months after the last Sham rTMS treatment.

Group Type SHAM_COMPARATOR

Transcranial Magnetic Stimulation, Repetitive

Intervention Type DEVICE

10 rTMS treatments (90% of motor threshold, 20 minutes, at 1 Hz) to specific right hemisphere area of brain cortex; 5 days per week for 2 weeks at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; or at the Neurology Department, Hospital of the University of Pennsylvania, Philadelphia, PA.

Interventions

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Transcranial Magnetic Stimulation, Repetitive

10 rTMS treatments (90% of motor threshold, 20 minutes, at 1 Hz) to specific right hemisphere area of brain cortex; 5 days per week for 2 weeks at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; or at the Neurology Department, Hospital of the University of Pennsylvania, Philadelphia, PA.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Right Handed
* Single, Left Hemisphere Cerebrovascular Stroke
* Must be at least 6 months poststroke onset
* Native Speaker of English
* Clinical Diagnosis of Aphasia

Exclusion Criteria

* Intracranial metallic body from prior neurosurgical procedure
* Implanted metallic devices: pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit or ventriculoperitoneal shunt
* Past history of seizure within 1 year
* Pregnancy
* History of substance abuse within last 6 months
Minimum Eligible Age

45 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Deafness and Other Communication Disorders (NIDCD)

NIH

Sponsor Role collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Boston University

OTHER

Sponsor Role lead

Responsible Party

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Margaret Naeser

Research Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Margaret A Naeser, Ph.D.

Role: STUDY_CHAIR

Department of Neurology, Boston University School of Medicine, Boston, MA

H B Coslett, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA

Alvaro Pascual-Leone, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Locations

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VA Boston Healthcare System, Jamaica Plain Campus, Boston University Aphasia Research Center (12-A), 150 So. Huntington Ave.

Boston, Massachusetts, United States

Site Status

Berenson-Allen Center for Noninvasive Brain Stimulation, 330 Brookline Ave, Kirstein Bldg., Dept. of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School

Boston, Massachusetts, United States

Site Status

Department of Neurology, Hospital of the University of Pennsylvania, 3 W. Gates Bldg.

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Martin PI, Naeser MA, Ho M, Treglia E, Kaplan E, Baker EH, Pascual-Leone A. Research with transcranial magnetic stimulation in the treatment of aphasia. Curr Neurol Neurosci Rep. 2009 Nov;9(6):451-8. doi: 10.1007/s11910-009-0067-9.

Reference Type BACKGROUND
PMID: 19818232 (View on PubMed)

Naeser MA, Martin PI, Treglia E, Ho M, Kaplan E, Bashir S, Hamilton R, Coslett HB, Pascual-Leone A. Research with rTMS in the treatment of aphasia. Restor Neurol Neurosci. 2010;28(4):511-29. doi: 10.3233/RNN-2010-0559.

Reference Type BACKGROUND
PMID: 20714075 (View on PubMed)

Hamilton RH, Chrysikou EG, Coslett B. Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation. Brain Lang. 2011 Jul;118(1-2):40-50. doi: 10.1016/j.bandl.2011.02.005. Epub 2011 Apr 2.

Reference Type BACKGROUND
PMID: 21459427 (View on PubMed)

Chrysikou EG, Hamilton RH. Noninvasive brain stimulation in the treatment of aphasia: exploring interhemispheric relationships and their implications for neurorehabilitation. Restor Neurol Neurosci. 2011;29(6):375-94. doi: 10.3233/RNN-2011-0610.

Reference Type BACKGROUND
PMID: 22124035 (View on PubMed)

Naeser MA, Martin PI, Ho M, Treglia E, Kaplan E, Bashir S, Pascual-Leone A. Transcranial magnetic stimulation and aphasia rehabilitation. Arch Phys Med Rehabil. 2012 Jan;93(1 Suppl):S26-34. doi: 10.1016/j.apmr.2011.04.026.

Reference Type BACKGROUND
PMID: 22202188 (View on PubMed)

Torres J, Drebing D, Hamilton R. TMS and tDCS in post-stroke aphasia: Integrating novel treatment approaches with mechanisms of plasticity. Restor Neurol Neurosci. 2013;31(4):501-15. doi: 10.3233/RNN-130314.

Reference Type BACKGROUND
PMID: 23719561 (View on PubMed)

Garcia G, Norise C, Faseyitan O, Naeser MA, Hamilton RH. Utilizing repetitive transcranial magnetic stimulation to improve language function in stroke patients with chronic non-fluent aphasia. J Vis Exp. 2013 Jul 2;(77):e50228. doi: 10.3791/50228.

Reference Type BACKGROUND
PMID: 23852365 (View on PubMed)

Naeser MA, Martin PI, Ho M, Treglia E, Kaplan E, Baker EH, and Pascual-Leone A. Transcranial Magnetic Stimulation and Aphasia Research. Book Chapter, Advances in the Neural Substrates of Language: Toward a Synthesis of Basic Science and Clinical Research. Vol 2: Language Processing in the Brain: Special Populations. Miriam Faust (Ed.), Malden, MA: Wiley-Blackwell, 2012.

Reference Type BACKGROUND

Martin PI, Naeser MA, Theoret H, Tormos JM, Nicholas M, Kurland J, Fregni F, Seekins H, Doron K, Pascual-Leone A. Transcranial magnetic stimulation as a complementary treatment for aphasia. Semin Speech Lang. 2004 May;25(2):181-91. doi: 10.1055/s-2004-825654.

Reference Type RESULT
PMID: 15118944 (View on PubMed)

Naeser MA, Martin PI, Nicholas M, Baker EH, Seekins H, Kobayashi M, Theoret H, Fregni F, Maria-Tormos J, Kurland J, Doron KW, Pascual-Leone A. Improved picture naming in chronic aphasia after TMS to part of right Broca's area: an open-protocol study. Brain Lang. 2005 Apr;93(1):95-105. doi: 10.1016/j.bandl.2004.08.004.

Reference Type RESULT
PMID: 15766771 (View on PubMed)

Naeser MA, Martin PI, Nicholas M, Baker EH, Seekins H, Helm-Estabrooks N, Cayer-Meade C, Kobayashi M, Theoret H, Fregni F, Tormos JM, Kurland J, Doron KW, Pascual-Leone A. Improved naming after TMS treatments in a chronic, global aphasia patient--case report. Neurocase. 2005 Jun;11(3):182-93. doi: 10.1080/13554790590944663.

Reference Type RESULT
PMID: 16006338 (View on PubMed)

Martin PI, Naeser MA, Ho M, Doron KW, Kurland J, Kaplan J, Wang Y, Nicholas M, Baker EH, Alonso M, Fregni F, Pascual-Leone A. Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS. Brain Lang. 2009 Oct;111(1):20-35. doi: 10.1016/j.bandl.2009.07.007. Epub 2009 Aug 19.

Reference Type RESULT
PMID: 19695692 (View on PubMed)

Naeser MA, Martin PI, Lundgren K, Klein R, Kaplan J, Treglia E, Ho M, Nicholas M, Alonso M, Pascual-Leone A. Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS. Cogn Behav Neurol. 2010 Mar;23(1):29-38. doi: 10.1097/WNN.0b013e3181bf2d20.

Reference Type RESULT
PMID: 20299861 (View on PubMed)

Hamilton RH, Sanders L, Benson J, Faseyitan O, Norise C, Naeser M, Martin P, Coslett HB. Stimulating conversation: enhancement of elicited propositional speech in a patient with chronic non-fluent aphasia following transcranial magnetic stimulation. Brain Lang. 2010 Apr;113(1):45-50. doi: 10.1016/j.bandl.2010.01.001. Epub 2010 Feb 16.

Reference Type RESULT
PMID: 20159655 (View on PubMed)

Naeser MA, Martin PI, Theoret H, Kobayashi M, Fregni F, Nicholas M, Tormos JM, Steven MS, Baker EH, Pascual-Leone A. TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia. Brain Lang. 2011 Dec;119(3):206-13. doi: 10.1016/j.bandl.2011.07.005. Epub 2011 Aug 23.

Reference Type RESULT
PMID: 21864891 (View on PubMed)

Turkeltaub PE, Coslett HB, Thomas AL, Faseyitan O, Benson J, Norise C, Hamilton RH. The right hemisphere is not unitary in its role in aphasia recovery. Cortex. 2012 Oct;48(9):1179-86. doi: 10.1016/j.cortex.2011.06.010. Epub 2011 Jun 30.

Reference Type RESULT
PMID: 21794852 (View on PubMed)

Medina J, Norise C, Faseyitan O, Coslett HB, Turkeltaub PE, Hamilton RH. Finding the Right Words: Transcranial Magnetic Stimulation Improves Discourse Productivity in Non-fluent Aphasia After Stroke. Aphasiology. 2012 Sep 1;26(9):1153-1168. doi: 10.1080/02687038.2012.710316. Epub 2012 Aug 29.

Reference Type RESULT
PMID: 23280015 (View on PubMed)

Harvey DY, Podell J, Turkeltaub PE, Faseyitan O, Coslett HB, Hamilton RH. Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation. Cogn Behav Neurol. 2017 Dec;30(4):133-144. doi: 10.1097/WNN.0000000000000141.

Reference Type DERIVED
PMID: 29256908 (View on PubMed)

Related Links

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http://www.bu.edu/naeser/aphasia

Aphasia Research Lab of Margaret A. Naeser, Ph.D., VA Boston Healthcare System and Dept. of Neurology, Boston University School of Medicine, Boston, MA

http://tmslab.org

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Dept. of Neurology, Harvard Medical School, Boston, MA

Other Identifiers

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R01DC005672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Boston Medical Ctr IRB-H22484

Identifier Type: OTHER

Identifier Source: secondary_id

VA Boston Healthcare IRB-1145

Identifier Type: OTHER

Identifier Source: secondary_id

NIH-DC05672

Identifier Type: -

Identifier Source: org_study_id

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