pBFS-guided iTBS Over the Superior Temporal Gyrus for Aphasia After Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
The objective of this trial is to evaluate the effectiveness and safeness of intermittent Theta Burst Stimulation (iTBS) over the left Superior Temporal Gyrus (STG), guided by personalized Brain Functional Sector (pBFS) technology, on language function recovery in patients with post-ischemic stroke aphasia.

Detailed Description
-----------------
Increasing evidence suggests that rTMS has been effective in treating various psychological and neurological diseases, including treating post-stroke symptoms. Using the personalized Brain Functional Sector (pBFS) technique, investigators could precisely identify individualized brain functional networks and the personalized language-related stimulation site based on the resting-state functional MRI data. The current study proposes to conduct a double-blinded, randomized and sham controlled trial, to investigate the efficacy and safety of pBFS-guided personalized rTMS intervention in post-stroke aphasic patients. Subjects will be randomly assigned to the following two groups: active intermittent TBS (iTBS) group, or a sham control group. The allocation ratio will be 1:1. The stimulation protocol consists of a 3-week treatment, with five consecutive days each week (totally 15 day-treatment) . The stimulation procedure will be assisted with real-time neuronavigation to ensure its precision.

Official Title
-----------------
Personalized Brain Functional Sector-guided Intermittent Theta Burst Stimulation Therapy Targeting at the Superior Temporal Gyrus for Aphasia After Ischemic Stroke: a RCT

Conditions
-----------------
Stroke, Ischemic, Aphasia

Intervention / Treatment
-----------------
* Device: active intermittent Theta Burst Stimulation
* Device: sham intermittent Theta Burst Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient's age ranges from 35 to 75 years old (including 35 and 75 years old); Meet the diagnostic criteria for acute ischemic stroke (diagnosed according to the Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke written by the American Heart Association/American Stroke Association in 2019 and the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018 compiled by the Neurology Branch of the Chinese Medical Association in 2018), with lesions in the left hemisphere, and a duration of ≥15 days and ≤3 months; Diagnosed as aphasia patient according to the Chinese version of Western Aphasia Battery (WAB), with a WAB-aphasia quotient of less than 93.8 points; First onset of stroke; Normal language function before the onset of stroke, and the patient's native language is Chinese with at least 6 years of education; Understand the trial and signed the informed consent form. Exclusion Criteria: Combined severe dysarthria (NIHSS item 10 score ≥2 points); Aphasia caused by bilateral hemisphere stroke, brain tumor, traumatic brain injury, Parkinson's disease, motor neuron disease, or other diseases； Patients with implanted electronic devices such as cardiac pacemakers, cochlear implants, or other metal foreign objects, or those with MRI contraindications such as claustrophobia or TMS treatment contraindications; History of epilepsy; Patient with concomitant severe systemic diseases affecting the heart, lungs, liver, kidneys, etc., and uncontrolled by conventional medication, as detected and confirmed through laboratory testing and examination； Patients with consciousness disorders (NIHSS 1(a) score ≥1); Patients with malignant hypertension; Patients with severe organic diseases, such as malignant tumors, with an expected survival time of less than 1 year; Patients with severe hearing, visual, cognitive impairment or inability to cooperate with the trial; Patients with severe depression, anxiety, or diagnosed with other mental illnesses that prevent them from completing the trial; Patients who have received other neuromodulation treatments such as TMS, transcranial electric stimulation, etc. in the 3 months prior to enrollment; Patients with a history of alcoholism, drug abuse, or other substance abuse; Patients with other abnormal findings that the researchers judge are not suitable for participation in this trial; Patients who are unable to complete follow-up due to geographical or other reasons; Women of childbearing age who are currently pregnant, breastfeeding, or planning or may become pregnant during the trial; Patients who are currently participating in other clinical trials.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active iTBS group<br>active iTBS combined with speech language therapy | Device: active intermittent Theta Burst Stimulation<br>* Each patient will receive two 600-pulse iTBS stimulations per day, parted by a 15-minute rest period (a total of 1200 pulses daily), for 3-week treatment, with five consecutive days each week.<br>|
| Sham Comparator: sham iTBS group<br>sham iTBS combined with speech language therapy | Device: sham intermittent Theta Burst Stimulation<br>* Each patient will receive two sham 600-pulse iTBS stimulations per day, parted by a 15-minute rest period (a total of 1200 pulses daily), for 3-week treatment, with five consecutive days each week.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Western Aphasia Battery scores | The first four subsets of the WAB (Spontaneous Speech, Auditory verbal comprehension, Repetition, Naming and word finding) will be used to evaluate the participants' language ability impairments. A Chinese adapted version of WAB will be used. The scores from all four subsets will be calculated as an Aphasia Quotient (ranging from 0 to 100), with lower Aphasia Quotients indicating poorer language abilities. | baseline, end of the 3-week therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Western Aphasia Battery scores | The first four subsets of the WAB (Spontaneous Speech, Auditory verbal comprehension, Repetition, Naming and word finding) will be used to evaluate the participants' language ability impairments. A Chinese adapted version of WAB will be used. The scores from all four subsets will be calculated as an Aphasia Quotient (ranging from 0 to 100), with lower Aphasia Quotients indicating poorer language abilities. | baseline, end of the 5-day therapy, 90 days after treatment initiation | 
| Boston Diagnostic Aphasia Examination Severity Ratings | The Boston Diagnostic Aphasia Examination (BDAE) Severity Ratings is a clinical tool used to evaluate the severity and type of aphasia in individuals. The assessment includes four domains: communication abilities, language content, speech sound production and response abilities.BDAE severity ratings range from level 1 to level 5, with higher scores indicating more severe aphasia. | baseline，end of the 3-week therapy，90 days after treatment initiation | 
| Token test | The Token Test is a language assessment tool used to evaluate a person's ability to understand spoken language and follow instructions. Each correct response in each task is awarded one point, typically. Different point values may be assigned based on the complexity of the task. The total score is calculated by adding up the accumulated scores across all tasks. The total scores range from 0 to 36, with higher scores indicating better language abilities. | baseline，end of the 3-week therapy，90 days after treatment initiation | 
| Chinese-version Stroke and Aphasia Quality of Life Scale 39-generic version (SAQOL-39g) | The SAQOL-39g is a quality of life assessment tool that is used to evaluate the impact of stroke and aphasia on a patient's quality of life. It consists of 39 items that cover a range of domains related to the patient's quality of life, such as communication, physical functioning, mood, and social support. The items are rated on a 5-point Likert scale ranging from not at all to very much, with higher scores indicating better quality of life. | baseline，end of the 3-week therapy，90 days after treatment initiation |