Effects of Neuronavigated Theta Burst Stimulation in Therapy of Post-stroke Aphasia

NCT ID: NCT05303649

Last Updated: 2024-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-02

Study Completion Date

2027-12-31

Brief Summary

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Aphasia is an impairment in the ability to express and/or understand language, commonly observed after stroke to the language dominant (left) hemisphere. Despite natural tendency to spontaneous functional recovery in the first months post stroke and language improvement due to application of behavioral speech and language therapy (SLT), many aphasic patients do not achieve satisfactory level of verbal communication. The aim of the planned study is to explore the potential of the noninvasive repetitive Transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for aphasia in addition to traditional behavioral therapy. In case of aphasia, studies on therapeutic effectiveness of rTMS aim to increase the activity of the language-dominant left cerebral hemisphere, which may be achieved in an indirect manner by inhibiting the activity of the opposite (right) hemisphere or in a direct manner by increasing the excitability of preserved language areas in the left hemisphere. In our study, we plan to administer the newest form of rTMS called Theta Burst Stimulation (TBS), which is safer than the conventional rTMS, even when used in the perilesional area. Computer-based neuronavigation system will be implemented to precisely localize stimulation targets, control administration of stimuli during rTMS sessions, and evaluate differences between participants regarding deviations from established stimulation points. 45 patients (all right-handed, polish native speakers, aged 18-75 years, diagnosed with non-fluent aphasia) will be enrolled in a randomized, double-blind, sham-controlled trial. Subjects will be randomly assigned to one of the three groups: 1) a group with excitatory intermittent TBS of the left hemisphere (iTBS group), 2) a group with inhibitory continuous TBS of the right hemisphere (cTBS group), 3) a group with sham TBS (sTBS group as a control group). Specific forms of stimulation will be carried out for three consecutive weeks (Monday to Friday; a total of 15 stimulation sessions). Immediately after each session of the stimulation, patients will undergo individual SLT. Assessment of language functioning will be carried out three times: before and after the therapy period, and 3 months after its completion. Results of the study will broaden knowledge about hemispherical mechanisms of language and speech recovery after stroke and provide insight into possibilities of their modulation for the purpose of post-stroke rehabilitation.

Detailed Description

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Conditions

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Stroke, Ischemic Aphasia Non Fluent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Intermittent TBS (iTBS) of the left hemisphere plus behavioral aphasia therapy

15 sessions of 200-second of iTBS over the pars triangularis of Broca's area in the left hemisphere (BA 45), preceding 45-minutes of behavioral aphasia therapy.

Group Type EXPERIMENTAL

Noninvasive transcranial brain stimulation: excitatory iTBS

Intervention Type DEVICE

600 pulses (3 pulses at 50 Hz given every 200 milliseconds in 2-second trains at 10-second intervals, delivered at 80% of active motor threshold) generated by Magstim Super Rapid2 stimulator equipped with a figure-of-eight coil applied over BA 45 Device: Magstim Co., Wales, UK.

Individual speech-language therapy (SLT)

Intervention Type BEHAVIORAL

45 minutes training tailored to every patient's deficits, abilities and needs. Exercises used during each therapeutic session include: expressions tasks (naming and sentence building), complex utterances comprehension tasks, reading and writing exercises. Training is administered using paper-and-pencil tasks and computerized aphasia therapy program AfaSystem (Harpo sp.zoo, Poznań, Poland).

Continuous TBS (cTBS) of the right hemisphere plus behavioral aphasia therapy

15 sessions of 40 seconds of cTBS over the pars triangularis of the right inferior frontal gyrus (BA 45 homologue), preceding 45-minutes of behavioral aphasia therapy.

Group Type EXPERIMENTAL

Noninvasive transcranial brain stimulation: inhibitory cTBS

Intervention Type DEVICE

600 pulses (3 pulses at 50 Hz, repeated at 5 Hz, delivered at 80% of active motor threshold) generated by Magstim Super Rapid2 stimulator equipped with a figure-of-eight coil applied over BA 45 homologue Device: Magstim Co., Wales, UK.

Individual speech-language therapy (SLT)

Intervention Type BEHAVIORAL

45 minutes training tailored to every patient's deficits, abilities and needs. Exercises used during each therapeutic session include: expressions tasks (naming and sentence building), complex utterances comprehension tasks, reading and writing exercises. Training is administered using paper-and-pencil tasks and computerized aphasia therapy program AfaSystem (Harpo sp.zoo, Poznań, Poland).

Sham TBS (sTBS) of the left hemisphere plus behavioral aphasia therapy

15 sessions of sham TBS over the pars triangularis of Broca's area in the left hemisphere (BA 45), preceding 45-minutes of behavioral aphasia therapy.

Group Type SHAM_COMPARATOR

Individual speech-language therapy (SLT)

Intervention Type BEHAVIORAL

45 minutes training tailored to every patient's deficits, abilities and needs. Exercises used during each therapeutic session include: expressions tasks (naming and sentence building), complex utterances comprehension tasks, reading and writing exercises. Training is administered using paper-and-pencil tasks and computerized aphasia therapy program AfaSystem (Harpo sp.zoo, Poznań, Poland).

Sham TBS simulating left hemispheric iTBS

Intervention Type DEVICE

Sham TMS coil positioned exactly like an active TMS coil resulting in a very good approximation of the auditory effects Device: Magstim Co., Wales, UK.

Interventions

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Noninvasive transcranial brain stimulation: excitatory iTBS

600 pulses (3 pulses at 50 Hz given every 200 milliseconds in 2-second trains at 10-second intervals, delivered at 80% of active motor threshold) generated by Magstim Super Rapid2 stimulator equipped with a figure-of-eight coil applied over BA 45 Device: Magstim Co., Wales, UK.

Intervention Type DEVICE

Noninvasive transcranial brain stimulation: inhibitory cTBS

600 pulses (3 pulses at 50 Hz, repeated at 5 Hz, delivered at 80% of active motor threshold) generated by Magstim Super Rapid2 stimulator equipped with a figure-of-eight coil applied over BA 45 homologue Device: Magstim Co., Wales, UK.

Intervention Type DEVICE

Individual speech-language therapy (SLT)

45 minutes training tailored to every patient's deficits, abilities and needs. Exercises used during each therapeutic session include: expressions tasks (naming and sentence building), complex utterances comprehension tasks, reading and writing exercises. Training is administered using paper-and-pencil tasks and computerized aphasia therapy program AfaSystem (Harpo sp.zoo, Poznań, Poland).

Intervention Type BEHAVIORAL

Sham TBS simulating left hemispheric iTBS

Sham TMS coil positioned exactly like an active TMS coil resulting in a very good approximation of the auditory effects Device: Magstim Co., Wales, UK.

Intervention Type DEVICE

Other Intervention Names

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Magstim Super Rapid2 Magstim Super Rapid2 Magstim Super Rapid2

Eligibility Criteria

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Inclusion Criteria

* First-ever left middle cerebral artery ischemic stroke (brain damage localization confirmed by magnetic resonance imaging, MRI)
* 3 or more months from the onset of stroke
* Non-fluent aphasia (confirmed in the BDAE test) with functional communication difficulties ranging from mild to significant (grades from 2 to 4 in ASRS), marked difficulties in naming, and relatively preserved everyday speech comprehension
* Native Polish speaker
* Right-handedness prior to stroke
* Signing of the informed consent for the participation in the study.

Exclusion Criteria

* Psychiatric and/or neurological comorbidity (e. g. dementia, depressive disorder, alcohol dependence)
* Diagnose of epilepsy or epileptic changes in EEG, also frequent losses of consciousness of unclear etiology which might suggest epileptic seizures
* History of any neurosurgical procedure around the head area
* 1.5 T MRI examination contraindications (metal elements in the body, e. g. implantable cardioverter-defibrillator, deep brain stimulation devices; claustrophobia)
* Regular intake of medication that could affect cortical excitability (e. g. antiepileptic or antipsychotic drugs, antidepressants, benzodiazepines) or medication influencing neuroplastic processes (e. g. dopamine)
* Significant cognitive impairment limiting patient's cooperation during assessment and behavioral aphasia therapy
* Visual deficits significantly hindering the perception of therapeutic tasks presented visually on a computer's screen
* New neurological episode (e. g. another brain stroke) or somatic illness (e. g. COVID-19) during the cycle of the therapy, requiring its interruption.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Psychiatry and Neurology, Warsaw

OTHER

Sponsor Role lead

Responsible Party

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Katarzyna Polanowska

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Katarzyna E Polanowska, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Psychiatry and Neurology, Warsaw, Poland

Locations

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Institute of Psychiatry and Neurology

Warsaw, Masovian Voivodeship, Poland

Site Status RECRUITING

Countries

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Poland

Central Contacts

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Katarzyna E Polanowska, PhD

Role: CONTACT

+48224582870

Szczepan Iwański, PhD

Role: CONTACT

+48224582870

Facility Contacts

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Katarzyna E Polanowska, PhD

Role: primary

+48224582870

References

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Harvey DY, Mass JA, Shah-Basak PP, Wurzman R, Faseyitan O, Sacchetti DL, DeLoretta L, Hamilton RH. Continuous theta burst stimulation over right pars triangularis facilitates naming abilities in chronic post-stroke aphasia by enhancing phonological access. Brain Lang. 2019 May;192:25-34. doi: 10.1016/j.bandl.2019.02.005. Epub 2019 Mar 11.

Reference Type BACKGROUND
PMID: 30870740 (View on PubMed)

Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

Reference Type BACKGROUND
PMID: 15664172 (View on PubMed)

Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.

Reference Type BACKGROUND
PMID: 31901449 (View on PubMed)

Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f.

Reference Type BACKGROUND
PMID: 21221011 (View on PubMed)

Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Screening questionnaire before TMS: an update. Clin Neurophysiol. 2011 Aug;122(8):1686. doi: 10.1016/j.clinph.2010.12.037. Epub 2011 Jan 11. No abstract available.

Reference Type BACKGROUND
PMID: 21227747 (View on PubMed)

Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

Reference Type BACKGROUND
PMID: 19833552 (View on PubMed)

Shah PP, Szaflarski JP, Allendorfer J, Hamilton RH. Induction of neuroplasticity and recovery in post-stroke aphasia by non-invasive brain stimulation. Front Hum Neurosci. 2013 Dec 24;7:888. doi: 10.3389/fnhum.2013.00888.

Reference Type BACKGROUND
PMID: 24399952 (View on PubMed)

Schlaug G, Marchina S, Wan CY. The use of non-invasive brain stimulation techniques to facilitate recovery from post-stroke aphasia. Neuropsychol Rev. 2011 Sep;21(3):288-301. doi: 10.1007/s11065-011-9181-y. Epub 2011 Aug 14.

Reference Type BACKGROUND
PMID: 21842404 (View on PubMed)

Szaflarski JP, Griffis J, Vannest J, Allendorfer JB, Nenert R, Amara AW, Sung V, Walker HC, Martin AN, Mark VW, Zhou X. A feasibility study of combined intermittent theta burst stimulation and modified constraint-induced aphasia therapy in chronic post-stroke aphasia. Restor Neurol Neurosci. 2018;36(4):503-518. doi: 10.3233/RNN-180812.

Reference Type BACKGROUND
PMID: 29889086 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21358599 (View on PubMed)

Ball LJ, Beukelman DR, Pattee GL. Communication effectiveness of individuals with amyotrophic lateral sclerosis. J Commun Disord. 2004 May-Jun;37(3):197-215. doi: 10.1016/j.jcomdis.2003.09.002.

Reference Type BACKGROUND
PMID: 15063143 (View on PubMed)

Other Identifiers

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IPiN_KP01

Identifier Type: -

Identifier Source: org_study_id

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