- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03651700
Transcranial Magnetic Stimulation and Constraint Induced Language Therapy for Chronic Aphasia
A Phase II, Randomized Blinded Study of the Effects of Transcranial Magnetic Stimulation and Constraint Induced Language Therapy for the Treatment of Chronic Aphasia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
TMS is a technique by which a brief electrical current is induced in brain tissue causing a brief suppression of the excitability of the underlying tissue; the technique, which was introduced in the 1980s and has been extensively used around the world, has been shown to transiently improve or disrupt specific cognitive operations. To achieve this end, a coil is positioned against the subject's head. The delivery of a single pulse begins with the discharge of current from a capacitor into a circular or figure-of-eight coil; this electrical current generates a brief magnetic field of up to 2.2 Tesla. As the pulse of electricity has a rise time of 0.2 ms. and a duration of 1 ms., the magnetic field changes in intensity quite rapidly. Because the magnetic field passes freely through the scalp, skull, and meninges, the flux in the magnetic field induces a small electric field in the brain that transiently alters neural activity.
TMS may be delivered in a variety of ways. The investigators propose to use 1 Hz TMS; that is, TMS pulses will be delivered at a frequency of 1/second. This style of TMS is assumed to be inhibitory in that it transiently suppresses the function of the cortex under the coil. Using the figure-of-eight coil to be employed here, TMS is thought to reduce activity in approximately 1 cubic cm. of cortex. Many investigators have employed TMS with a frequency of 1 Hz for periods of 20 minutes and longer; mild behavioral deficits are often present for several minutes in these studies.
The baseline phase will consist of 3 sessions, each lasting 1-2 hours depending on the stamina of the subject. The point of the baseline testing is to characterize the subject's language function. To that end, a number of standard language and neuropsychological tasks will be administered. These include the Western Aphasia Battery, Pyramids and Palm Trees test, Figural Fluency Test, word and non-word repetition tasks, the Nicholas and Brookshire Narratives, CILT stimulus naming, and Northwestern Assessment of Verbs and Sentences. Additionally, during the baseline, subjects will undergo MRI of the brain or, if they have a contraindication to MRI, a CAT scan of the head. No contrast will be used.
In the treatment phase, there will be 10 TMS sessions over 2 consecutive weeks in which 20 minutes (1200 pulses) of 1 Hz TMS at 90% motor threshold will be delivered to the inferior pars triangularis. Each TMS treatment session will be immediately followed by a 60-90 minute session of CILT
There will be two 3-month post-treatment visits and two 6-month post-treatment visits in which the full battery of language and cognitive assessments will be repeated. Subjects who are able to undergo MRI scanning will have anatomic and fMRI scans at the first 6-month post-treatment visit.
The investigators will pair TMS with CILT which has been shown to have positive outcomes in post-stroke aphasia. CILT invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures. The investigators will use a dual card-matching task modeled after Maher et al. As in the original CILT design, the participant interacts verbally with a conversational partner (here, the speech language pathologist), in turn requesting a card of given description and complying with the partner's request. In this way, the treatment targets both production and comprehension. Moreover, as verbal targets increase in linguistic complexity across the protocol ("a ball", "throw a ball"; "Do you have a ball"?), a variety of lexical and phrasal structures are targeted. Studies of CILT have reported gains on multiple language behaviors, supporting its broad engagement of the language network.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Samuel Cason, MA
- Phone Number: 215-573-4336
- Email: samuel.cason@pennmedicine.upenn.edu
Study Contact Backup
- Name: Principal Investigator
- Phone Number: 215-349-8585
- Email: hbc@pennmedicine.upenn.edu
Study Locations
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Clinical evidence and MRI or CT verification of a single left hemisphere stroke with moderate to severe aphasia.
- Suffered their stroke at least 6 months prior to their testing
- Must be able to understand the nature of the study, and give informed consent
Exclusion Criteria:
- Multiple strokes (excluding small lacunar strokes) as defined by brain imaging
- History of substance abuse
- Previous head trauma with loss of consciousness for more than 5 minutes
- Psychiatric illness (We note that subjects will be assessed with the 15-item Geriatric Depression scale. Because depression is very difficult to evaluate in aphasic subjects, potential subjects will not be excluded on the basis of the depression score)
- Chronic exposure to medications that might be expected to have lasting consequences for the central nervous system (e.g. haloperidol, dopaminergics)
- History of or neuropsychological findings suggestive of dementia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active TMS
There will be 10 TMS sessions over 2 consecutive weeks in which 20 minutes (1200 pulses) of 1 Hz active TMS will be delivered to the inferior pars triangular.
Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT).
|
60-90 minutes of CILT will be administered during each treatment session
Other Names:
Active TMS will be at 90% motor threshold
|
Sham Comparator: Sham TMS
There will be 10 TMS sessions over 2 consecutive weeks in which 20 minutes (1200 pulses) of 1 Hz sham TMS will be delivered to the inferior pars triangular.
Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field.
Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT).
|
60-90 minutes of CILT will be administered during each treatment session
Other Names:
Sham TMS will be administered
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in WAB-AQ
Time Frame: 6-months post-treatment
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Overall change in Western Aphasia Battery - Aphasia Quotient (WAB-AQ) between the first baseline visit and the 6-month follow-up visit
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6-months post-treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in PNT
Time Frame: 6-months post-treatment
|
Change in naming accuracy on the Philadelphia Naming Test (PNT) between the first baseline visit and the 6-month follow-up visit.
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6-months post-treatment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: H. Branch Coslett, MD, University of Pennsylvania
Publications and helpful links
General Publications
- 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.
- Seniow J, Waldowski K, Lesniak M, Iwanski S, Czepiel W, Czlonkowska A. Transcranial magnetic stimulation combined with speech and language training in early aphasia rehabilitation: a randomized double-blind controlled pilot study. Top Stroke Rehabil. 2013 May-Jun;20(3):250-61. doi: 10.1310/tsr2003-250.
- Kakuda W, Abo M, Shimizu M, Sasanuma J, Okamoto T, Yokoi A, Taguchi K, Mitani S, Harashima H, Urushidani N, Urashima M; NEURO Investigators. A multi-center study on low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis in post-stroke patients. J Neuroeng Rehabil. 2012 Jan 20;9(1):4. doi: 10.1186/1743-0003-9-4.
- Shewan CM, Kertesz A. Reliability and validity characteristics of the Western Aphasia Battery (WAB). J Speech Hear Disord. 1980 Aug;45(3):308-24. doi: 10.1044/jshd.4503.308.
- Nicholas LE, Brookshire RH. A system for quantifying the informativeness and efficiency of the connected speech of adults with aphasia. J Speech Hear Res. 1993 Apr;36(2):338-50. doi: 10.1044/jshr.3602.338.
- Pulvermuller F, Neininger B, Elbert T, Mohr B, Rockstroh B, Koebbel P, Taub E. Constraint-induced therapy of chronic aphasia after stroke. Stroke. 2001 Jul;32(7):1621-6. doi: 10.1161/01.str.32.7.1621.
- 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.
- Szaflarski JP, Vannest J, Wu SW, DiFrancesco MW, Banks C, Gilbert DL. Excitatory repetitive transcranial magnetic stimulation induces improvements in chronic post-stroke aphasia. Med Sci Monit. 2011 Feb 25;17(3):CR132-9. doi: 10.12659/msm.881446.
- 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.
- Weiduschat N, Thiel A, Rubi-Fessen I, Hartmann A, Kessler J, Merl P, Kracht L, Rommel T, Heiss WD. Effects of repetitive transcranial magnetic stimulation in aphasic stroke: a randomized controlled pilot study. Stroke. 2011 Feb;42(2):409-15. doi: 10.1161/STROKEAHA.110.597864. Epub 2010 Dec 16.
- Howard, D., & Patterson, K. E. (1992). The Pyramids and Palm Trees Test: A Test of Semantic Access from Words and Pictures. Thames Valley Test Company. Retrieved from books.google.com/books?id=dykONQAACAAJ
- Ruff, R. M. (1996). Ruff figural fluency test: professional manual. Psychological Assessment Resources.
- Maher LM, Kendall D, Swearengin JA, Rodriguez A, Leon SA, Pingel K, Holland A, Rothi LJ. A pilot study of use-dependent learning in the context of Constraint Induced Language Therapy. J Int Neuropsychol Soc. 2006 Nov;12(6):843-52. doi: 10.1017/S1355617706061029.
- Barthel, G., Meinzer, M., Djundja, D., & Rockstroh, B. (2008). Intensive language therapy in chronic aphasia: Which aspects contribute most? Aphasiology, 22(4), 408-421.
- Goral M, Kempler D. TRAINING VERB PRODUCTION IN COMMUNICATIVE CONTEXT: EVIDENCE FROM A PERSON WITH CHRONIC NON-FLUENT APHASIA. Aphasiology. 2009 Dec 12;23(12):1383-1397. doi: 10.1080/02687030802235203.
- Meinzer M, Rodriguez AD, Gonzalez Rothi LJ. First decade of research on constrained-induced treatment approaches for aphasia rehabilitation. Arch Phys Med Rehabil. 2012 Jan;93(1 Suppl):S35-45. doi: 10.1016/j.apmr.2011.06.040.
- Abo M, Kakuda W, Watanabe M, Morooka A, Kawakami K, Senoo A. Effectiveness of low-frequency rTMS and intensive speech therapy in poststroke patients with aphasia: a pilot study based on evaluation by fMRI in relation to type of aphasia. Eur Neurol. 2012;68(4):199-208. doi: 10.1159/000338773. Epub 2012 Aug 29.
- Avenanti A, Coccia M, Ladavas E, Provinciali L, Ceravolo MG. Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial. Neurology. 2012 Jan 24;78(4):256-64. doi: 10.1212/WNL.0b013e3182436558. Epub 2012 Jan 11.
- Barwood CH, Murdoch BE, Riek S, O'Sullivan JD, Wong A, Lloyd D, Coulthard A. Long term language recovery subsequent to low frequency rTMS in chronic non-fluent aphasia. NeuroRehabilitation. 2013;32(4):915-28. doi: 10.3233/NRE-130915.
- Barwood CHS, Murdoch BE, Whelan BM, Lloyd D, Riek S, O'Sullivan JD, Coulthard A, Wong A. Improved receptive and expressive language abilities in nonfluent aphasic stroke patients after application of rTMS: an open protocol case series. Brain Stimul. 2012 Jul;5(3):274-286. doi: 10.1016/j.brs.2011.03.005. Epub 2011 Apr 13.
- 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. Erratum In: Brain Lang.2010 May;113(2):101.
- Hara T, Abo M, Kobayashi K, Watanabe M, Kakuda W, Senoo A. Effects of low-frequency repetitive transcranial magnetic stimulation combined with intensive speech therapy on cerebral blood flow in post-stroke aphasia. Transl Stroke Res. 2015 Oct;6(5):365-74. doi: 10.1007/s12975-015-0417-7. Epub 2015 Aug 7.
- Kakuda W, Abo M, Momosaki R, Morooka A. Therapeutic application of 6-Hz-primed low-frequency rTMS combined with intensive speech therapy for post-stroke aphasia. Brain Inj. 2011;25(12):1242-8. doi: 10.3109/02699052.2011.608212. Epub 2011 Sep 8.
- Kakuda W, Abo M, Uruma G, Kaito N, Watanabe M. Low-frequency rTMS with language therapy over a 3-month period for sensory-dominant aphasia: case series of two post-stroke Japanese patients. Brain Inj. 2010;24(9):1113-7. doi: 10.3109/02699052.2010.494587.
- Khedr EM, Abo El-Fetoh N, Ali AM, El-Hammady DH, Khalifa H, Atta H, Karim AA. Dual-hemisphere repetitive transcranial magnetic stimulation for rehabilitation of poststroke aphasia: a randomized, double-blind clinical trial. Neurorehabil Neural Repair. 2014 Oct;28(8):740-50. doi: 10.1177/1545968314521009. Epub 2014 Feb 6.
- Kindler J, Schumacher R, Cazzoli D, Gutbrod K, Koenig M, Nyffeler T, Dierks T, Muri RM. Theta burst stimulation over the right Broca's homologue induces improvement of naming in aphasic patients. Stroke. 2012 Aug;43(8):2175-9. doi: 10.1161/STROKEAHA.111.647503. Epub 2012 May 10.
- Martin PI, Treglia E, Naeser MA, Ho MD, Baker EH, Martin EG, Bashir S, Pascual-Leone A. Language improvements after TMS plus modified CILT: Pilot, open-protocol study with two, chronic nonfluent aphasia cases. Restor Neurol Neurosci. 2014;32(4):483-505. doi: 10.3233/RNN-130365.
- 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.
- 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.
- 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.
- 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.
- Thiel A, Hartmann A, Rubi-Fessen I, Anglade C, Kracht L, Weiduschat N, Kessler J, Rommel T, Heiss WD. Effects of noninvasive brain stimulation on language networks and recovery in early poststroke aphasia. Stroke. 2013 Aug;44(8):2240-6. doi: 10.1161/STROKEAHA.111.000574. Epub 2013 Jun 27.
- Waldowski K, Seniow J, Lesniak M, Iwanski S, Czlonkowska A. Effect of low-frequency repetitive transcranial magnetic stimulation on naming abilities in early-stroke aphasic patients: a prospective, randomized, double-blind sham-controlled study. ScientificWorldJournal. 2012;2012:518568. doi: 10.1100/2012/518568. Epub 2012 Nov 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 831532-chbdfejh
- R01DC016800 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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