Transcranial Magnetic Stimulation to Improve Speech in Aphasia

Aphasia Clinical Trial

Official title:

Transcranial Magnetic Stimulation to Improve Speech

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00608582
• Other study ID #: NIH-DC05672
• Secondary ID: R01DC005672Bosto
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2008
• Last updated: January 29, 2015
• Start date: July 2002
• Est. completion date: June 2013

Study information

• Verified date: January 2015
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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. Patients are studied with overt naming fMRI brain scan pre-and post-rTMS at the Boston University Center for Biomedical Imaging.

RESEARCH PLAN AND METHODS:

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. We plan to study 20 nonfluent aphasia patients (>6 Mo. poststroke). An additional 20 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 (and overt naming fMRI scans) are obtained pre- and post- rTMS. All fMRI scans are covered under the PI's VA Merit Review Grant.

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 Naming subtests and Spontaneous Speech (cookie theft picture description) from the BDAE. Naming ability for Snodgrass & Vanderwart (S&V, 1980) pictures is also tested at Baseline. 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). S&V 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 Baseline S&V Naming), immediately following 10 minutes of rTMS to suppress that cortical area, is considered to be the Best Response ROI for that patient. We have observed that suppression of R post. BA 45 to be the Best Response area in 9 previous aphasia cases. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• Right Handed

• Single, Left Hemisphere Cerebrovascular Stroke

• Must be 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aphasia
• Cerebrovascular Stroke
• Stroke

Intervention

Device:
• 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.

Locations

Country	Name	City	State
United States	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	VA Boston Healthcare System, Jamaica Plain Campus, Boston University Aphasia Research Center (12-A), 150 So. Huntington Ave.	Boston	Massachusetts
United States	Department of Neurology, Hospital of the University of Pennsylvania, 3 W. Gates Bldg.	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
Boston University	Harvard Medical School, National Institute on Deafness and Other Communication Disorders (NIDCD), University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (8)

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 — View Citation

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 — View Citation

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. Review. — View Citation

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. Review. — View Citation

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/ — View Citation

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 rep — View Citation

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. Brai — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of pictures named on the Boston Naming Test, and naming subtests of the Boston Diagnostic Aphasia Exam		2 months and 6 months after the completion of a series of TMS treatments	No
Secondary	Number of words per longest phrase length, propositional speech, BDAE		2 months and 6 months after completion of a series of TMS treatments	No

External Links

•   Aphasia Research Lab of Margaret A. Naeser, Ph.D., VA Boston Healthcare System and Dept. of Neurology, Boston University School of Medicine, Boston, MA
•   Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Dept. of Neurology, Harvard Medical School, Boston, MA