Clinical trial NCT05303649: Effects of Neuronavigated Theta Burst Stimulation in Therapy of Post-stroke Aphasia
Official title: Effects of Neuronavigated Theta Burst Stimulation in Therapy of Post-stroke Aphasia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke, Ischemic
Aphasia Non Fluent
Keywords: Aphasia
Stroke
Theta Burst Stimulation
Therapy
Rehabilitation
Noninvasive Transcranial Brain Stimulation
Lead sponsor: Institute of Psychiatry and Neurology, Warsaw
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from pre-treatment assessment in the performance on a picture naming task
timeFrame: Pre-treatment assessment (within 2 days before starting the intervention), post-treatment assessment (within 2 days of completing the 15 days intervention)
measure: Change from pre-treatment in the performance on the picture naming task at 3 months post-therapy (follow up assessment)
timeFrame: Pre-treatment and 3 months follow-up (post-treatment) assessment
measure: Change from post-treatment in the performance on the picture naming task at 3 months post-therapy
timeFrame: Post-treatment and 3 months follow-up assessment
measure: Change from pre-treatment assessment in the performance on a scene description task of three visually presented scenes
timeFrame: Pre-treatment assessment, post-treatment assessment (within 2 days of completing the 15 days intervention)
measure: Change from pre-treatment in the scene description task at 3 months post-therapy
timeFrame: Pre-treatment and 3 months follow-up
measure: Change from post-treatment in the scene description task at 3 months post-therapy
timeFrame: Post-treatment and 3 months follow-up
measure: Change from pre-treatment on the semantic fluency task
timeFrame: Pre-treatment and post-treatment (within 2 days of completing the 15 days intervention)
measure: Change from pre-treatment on the semantic fluency task at 3 months post-therapy
timeFrame: Pre-treatment and 3 months follow-up
measure: Change from post-treatment on the semantic fluency task at 3 months post-therapy
timeFrame: Post-treatment and 3 months follow-up
Secondary outcomes:
measure: Modified Communication Effectiveness Index (CETI)
timeFrame: Pre-treatment, post-treatment (within 2 days of completing the 15 day intervention) and on 3-month follow-up
Other outcomes:
measure: The Polish version of short form of the Boston Diagnostic Aphasia Examination (BDAE)
timeFrame: Screening appointment (pre-enrollment assessment)
Locations:
city: Warsaw
country: Poland
facility: Institute of Psychiatry and Neurology
state: Masovian Voivodeship
Study officials:
affiliation: Institute of Psychiatry and Neurology, Warsaw, Poland
name: Katarzyna E Polanowska, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
citation: 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.