Aphasia, Cerebrovascular Stroke
Conditions
Keywords
Transcranial Magnetic Stimulation, Repetitive, TMS, Treat Naming, Aphasia, Chronic Stroke, Randomized, Controlled Trial
Brief 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.
Detailed 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. 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.
Interventions
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.
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Picture Naming | Baseline and 2 months after the last rTMS treatment session | Pictures named correctly on Boston Naming Test (BNT), First 20 Pictures |
| Phrase Length | Baseline and 2 months after the last rTMS treatment session | Longest Number of Words per Phrase Length, for elicited propositional speech for BDAE Cookie Theft Picture Description |
Countries
United States
Participant flow
Recruitment details
July 2002-March 2013. Recruited in hospital setting and outreach with affiliated and local clinics VA Boston Healthcare System, Boston, MA; Hospital of the University of Pennsylvania, Philadelphia, PA
Pre-assignment details
Assessed for eligibility by telephone screen, or in-office visit. Assessment included review of medical history. Total Excluded (n = 38) Not meeting inclusion criteria (n = 31) Declined to participate (n = 2) Other reasons (n = 5)
Participants by arm
| Arm | Count |
|---|---|
| Real rTMS These patients receive a series of 10 Real rTMS treatments, only. There is pre-testing, and post-testing at 2 months after the last Real rTMS treatment.
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. | 14 |
| Sham rTMS These patients receive a series of 10 Sham rTMS treatments, which are identical to the Real rTMS treatments. However, no magnetic pulse is emitted from the coil.
The patients then receive a series of 10 Real rTMS treatments. There is pre-testing, and post-testing at 2 months after the last Real rTMS treatment.
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. | 11 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early stage Design Change | 0 | 3 |
| Overall Study | Illicit Drug Use | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | No Best Response in Phase 1 located | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Real rTMS | Sham rTMS |
|---|---|---|---|
| Age, Continuous | 59.28 years STANDARD_DEVIATION 9.1 | 58.1 years STANDARD_DEVIATION 7.6 | 60.8 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 14 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 5 Participants | 3 Participants | 2 Participants |
| Gender Male | 20 Participants | 11 Participants | 9 Participants |
| Months Poststroke Onset | 59 months STANDARD_DEVIATION 39 | 66 months STANDARD_DEVIATION 40 | 51 months STANDARD_DEVIATION 37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 13 Participants | 11 Participants |
| Region of Enrollment United States | 25 Participants | 14 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 11 |
| serious Total, serious adverse events | 0 / 14 | 0 / 11 |
Outcome results
Phrase Length
Longest Number of Words per Phrase Length, for elicited propositional speech for BDAE Cookie Theft Picture Description
Time frame: Baseline and 2 months after the last rTMS treatment session
Population: Chronic Stroke Patients with Aphasia who received either Real rTMS or Sham rTMS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real rTMS | Phrase Length | Baseline | 5.2 number of words per phrase length | Standard Deviation 3.05 |
| Real rTMS | Phrase Length | 2 Mo. Post rTMS | 5.7 number of words per phrase length | Standard Deviation 3.02 |
| Sham rTMS | Phrase Length | Baseline | 5.285 number of words per phrase length | Standard Deviation 3.35 |
| Sham rTMS | Phrase Length | 2 Mo. Post rTMS | 5.0 number of words per phrase length | Standard Deviation 3 |
Picture Naming
Pictures named correctly on Boston Naming Test (BNT), First 20 Pictures
Time frame: Baseline and 2 months after the last rTMS treatment session
Population: Chronic Stroke Patients with Aphasia who receive either a Real rTMS series or a Sham rTMS series
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real rTMS | Picture Naming | Baseline | 10.3 number of pictures | Standard Deviation 6.11 |
| Real rTMS | Picture Naming | 2 Mo. Post rTMS | 12.1 number of pictures | Standard Deviation 5.55 |
| Sham rTMS | Picture Naming | 2 Mo. Post rTMS | 11.14 number of pictures | Standard Deviation 3.24 |
| Sham rTMS | Picture Naming | Baseline | 12.57 number of pictures | Standard Deviation 5.88 |