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

Stroke, Ischemic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05303649
• Other study ID #: IPiN_KP01
• Status: Recruiting
• Phase: N/A
• Start date: September 2, 2022
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Institute of Psychiatry and Neurology, Warsaw
• Contact: Katarzyna E Polanowska, PhD
• Phone: +48224582870
• Email: kpolanowska[@]ipin.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aphasia
• Aphasia Non Fluent
• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Intervention

Device:
• 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.
• 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.

Behavioral:
• 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, Poznan, Poland).

Device:
• 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.

Locations

Country	Name	City	State
Poland	Institute of Psychiatry and Neurology	Warsaw	Masovian Voivodeship

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Psychiatry and Neurology, Warsaw

Country where clinical trial is conducted

Poland, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Clin Neurophysiol. 2020 May;131(5):1168-1169. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Polish version of short form of the Boston Diagnostic Aphasia Examination (BDAE)	Assesses the linguistic skills of adults with aphasia. This provides information for the diagnosis of the type of aphasia. Includes the six-point Goodglass and Kaplan's Aphasia Severity Rating Scale (ASRS; 0-5 points - lower score means more severe language impairment).	Screening appointment (pre-enrollment assessment)
Primary	Change from pre-treatment assessment in the performance on a picture naming task	Total number of correctly named items (assessed: accuracy and speed of naming) from a set of 250 visually presented objects (200 noun names and 50 verb names; stimuli included in the set are diversified with regard to the articulation difficulty of corresponding words and their usage frequency in everyday speech).	Pre-treatment assessment (within 2 days before starting the intervention), post-treatment assessment (within 2 days of completing the 15 days intervention)
Primary	Change from pre-treatment in the performance on the picture naming task at 3 months post-therapy (follow up assessment)	Total number of correctly named items from a set of 250 visually presented objects.	Pre-treatment and 3 months follow-up (post-treatment) assessment
Primary	Change from post-treatment in the performance on the picture naming task at 3 months post-therapy	Total number of correctly named items from a set of 250 visually presented objects.	Post-treatment and 3 months follow-up assessment
Primary	Change from pre-treatment assessment in the performance on a scene description task of three visually presented scenes	(assessed: length and correctness of utterances).	Pre-treatment assessment, post-treatment assessment (within 2 days of completing the 15 days intervention)
Primary	Change from pre-treatment in the scene description task at 3 months post-therapy	Oral description of three visually presented scenes (assessed: length and correctness of utterances).	Pre-treatment and 3 months follow-up
Primary	Change from post-treatment in the scene description task at 3 months post-therapy	Oral description of three visually presented scenes (assessed: length and correctness of utterances).	Post-treatment and 3 months follow-up
Primary	Change from pre-treatment on the semantic fluency task	Producing within a minute as many words as possible from 3 semantic categories: animals, fruit, clothes; assessed: total number of correctly generated items.	Pre-treatment and post-treatment (within 2 days of completing the 15 days intervention)
Primary	Change from pre-treatment on the semantic fluency task at 3 months post-therapy	Total number of correctly generated items such as animals, fruits, clothes.	Pre-treatment and 3 months follow-up
Primary	Change from post-treatment on the semantic fluency task at 3 months post-therapy	Total number of correctly generated items such as animals, fruits, clothes.	Post-treatment and 3 months follow-up
Secondary	Modified Communication Effectiveness Index (CETI)	A questionnaire to complete by researcher and family member/caregiver. Contains descriptions of ten communication situations, patients' performance in each of them is assessed on a Likert-type scale (from 0 to 7). Higher score means better functional communication.	Pre-treatment, post-treatment (within 2 days of completing the 15 day intervention) and on 3-month follow-up