Effectiveness of Theta Burst Stimulation For Upper and Lower Extremity Recovery in Stroke
Effects of Different Theta Burst Stimulation Protocols Combined With Conventional Rehabilitation on Upper and Lower Extremity Motor Recovery in Patients With Early-Stage Stroke
This single-center, single-blind, randomized, sham-controlled clinical trial will include 60 patients aged >45 years who are within 3 months of a first-ever middle cerebral artery ischemic stroke. Participants will be randomized into four groups: coupled TBS (contralesional cTBS followed by ipsilesional iTBS), cTBS plus sham iTBS, sham cTBS plus iTBS, or sham TBS. TBS will be delivered over the primary motor cortex for 10 sessions over 2 weeks. Stimulation intensity will be set at 80% of the resting motor threshold determined using EMG-guided motor evoked potentials. Each cTBS and iTBS application will consist of 600 pulses. All participants will additionally receive standardized conventional rehabilitation for at least 4 weeks.
The primary outcome will be upper-extremity motor recovery assessed using the motor domain of the Fugl-Meyer Assessment. Secondary outcomes will include lower-extremity motor recovery, spasticity, sensory function, cortical excitability, functional ambulation, activities of daily living, and stroke-specific quality of life. Assessments will be performed at baseline, after the 2-week intervention, and at 1-month post-treatment follow-up.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Fatma Melis Ertuğrul Öztürk, Resident
- Phone Number: 03127970000
- Email: melis.ertugrul@hotmail.com
Study Locations
-
-
Yenimahalle
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Ankara, Yenimahalle, Turkey (Türkiye), 06170
- Recruiting
- Ankara Etlik Şehir Hastanesi
-
Contact:
- Fatma Melis Ertuğrul Öztürk, Resident
- Phone Number: 03127970000
- Email: melis.ertugrul@hotmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of ischemic stroke due to middle cerebral artery (MCA) occlusion confirmed by magnetic resonance imaging (MRI).
- Within the first 3 months after stroke.
- First-ever stroke.
- Age ≥45 years.
- Brunnstrom stage 1, 2, or 3 for the upper extremity and hand.
- No previous physical therapy after the current stroke.
- Ability to maintain at least minimal semi-sitting balance.
- Medically and neurologically stable.
- Mini-Mental State Examination score >24.
- Native Turkish speaker who voluntarily agrees to participate and provides written informed consent.
Exclusion Criteria:
- History of epilepsy.
- Presence of a pacemaker.
- Pregnancy.
- Neurological disease other than stroke.
- Metallic implants in the brain or scalp, including cochlear implants.
- History of brain surgery.
- Comorbid disease that may significantly impair general health, such as heart f-failure or chronic obstructive pulmonary disease, and/or severe infection.
- Diagnosis of malignancy.
- Peripheral nerve injury and/or musculoskeletal disorder affecting motor function of the upper or lower extremities, such as fracture.
- Cardiac arrhythmia.
- Aphasia, spatial neglect, or visual field loss.
- Visual or hearing impairment that prevents communication.
- Alcohol and/or drug dependence.
- Refusal to participate or failure to provide informed consent.
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 |
|---|---|
|
Experimental: Coupled TBS Group
Participants will receive contralesional continuous theta burst stimulation (cTBS) followed by ipsilesional intermittent theta burst stimulation (iTBS) within the same session. Ten sessions will be administered over 2 weeks in addition to standardized conventional rehabilitation. |
Continuous theta burst stimulation will be applied over the contralesional primary motor cortex (M1) at 80% of the resting motor threshold. A total of 600 pulses will be delivered over 40 seconds as triplets at 50 Hz repeated every 200 ms. Intermittent theta burst stimulation will be applied over the ipsilesional primary motor cortex (M1) at 80% of the resting motor threshold. A total of 600 pulses will be delivered over approximately 190 seconds using 2-second trains repeated every 10 seconds. |
|
Experimental: cTBS + Sham iTBS Group
Participants will receive contralesional continuous theta burst stimulation (cTBS) followed by ipsilesional sham intermittent theta burst stimulation (sham iTBS) within the same session. Ten sessions will be administered over 2 weeks in addition to standardized conventional rehabilitation. |
Continuous theta burst stimulation will be applied over the contralesional primary motor cortex (M1) at 80% of the resting motor threshold. A total of 600 pulses will be delivered over 40 seconds as triplets at 50 Hz repeated every 200 ms. Sham intermittent theta burst stimulation will be delivered over the ipsilesional primary motor cortex using a sham coil for approximately 190 seconds. |
|
Experimental: Sham cTBS + iTBS Group
Participants will receive contralesional sham continuous theta burst stimulation (sham cTBS) followed by ipsilesional intermittent theta burst stimulation (iTBS) within the same session. Ten sessions will be administered over 2 weeks in addition to standardized conventional rehabilitation. |
Intermittent theta burst stimulation will be applied over the ipsilesional primary motor cortex (M1) at 80% of the resting motor threshold. A total of 600 pulses will be delivered over approximately 190 seconds using 2-second trains repeated every 10 seconds. Sham continuous theta burst stimulation will be delivered over the contralesional primary motor cortex using a sham coil for 40 seconds. |
|
Sham Comparator: Sham TBS Group
Participants will receive contralesional sham continuous theta burst stimulation (sham cTBS) followed by ipsilesional sham intermittent theta burst stimulation (sham iTBS) within the same session. Ten sessions will be administered over 2 weeks in addition to standardized conventional rehabilitation. |
Sham intermittent theta burst stimulation will be delivered over the ipsilesional primary motor cortex using a sham coil for approximately 190 seconds. Sham continuous theta burst stimulation will be delivered over the contralesional primary motor cortex using a sham coil for 40 seconds. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Upper Extremity Motor Function Assessed by the Fugl-Meyer Assessment - Upper Extremity Motor Subscale (FMA-UE)
Time Frame: Baseline, Week 2, and Week 6
|
Upper extremity motor function will be assessed using the motor subsection of the Fugl-Meyer Assessment. The FMA-UE motor score ranges from 0 to 66, with higher scores indicating better upper extremity motor function. Each item is scored on a 3-point ordinal scale: 0 = cannot perform, 1 = performs partially, and 2 = performs fully |
Baseline, Week 2, and Week 6
|
|
Change in Lower Extremity Motor Function Assessed by the Fugl-Meyer Assessment - Lower Extremity Motor Subscale
Time Frame: Baseline, Week 2, and Week 6
|
Lower extremity motor recovery will be assessed using the lower extremity motor subsection of the Fugl-Meyer Assessment. |
Baseline, Week 2, and Week 6
|
|
Change in Motor Recovery Stage Assessed by the Brunnstrom Motor Recovery Stages
Time Frame: Baseline, Week 2, and Week 6
|
Motor recovery of the upper and lower extremities will be evaluated using the Brunnstrom Motor Recovery Stages. Each assessed region is rated separately from stage I (1) to stage VI (6), with higher stages indicating better motor recovery. |
Baseline, Week 2, and Week 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Spasticity Assessed by the Modified Ashworth Scale
Time Frame: Baseline, Week 2, and Week 6
|
Spasticity of the upper and lower extremities will be assessed using the Modified Ashworth Scale (MAS). Scores range from 0 (no increase in muscle tone) to 4 (rigidity in flexion or extension), with six ordinal categories: 0, 1, 1+, 2, 3, and 4. Higher scores indicate greater muscle tone and resistance to passive movement, representing a worse outcome. |
Baseline, Week 2, and Week 6
|
|
Change in Sensory Function Assessed by the Fugl-Meyer Assessment - Sensory Subscale
Time Frame: Baseline, Week 2, and Week 6
|
Sensory function of the upper and lower extremities will be assessed using the sensory subsection of the Fugl-Meyer Assessment. This subsection evaluates light touch and joint position sense, with each item scored on a three-point ordinal scale (0-2). The combined sensory score for the upper and lower extremities ranges from 0 to 24, with higher scores indicating better sensory function. |
Baseline, Week 2, and Week 6
|
|
Change in Cortical Excitability Assessed by Motor Evoked Potential Amplitude
Time Frame: Baseline, Week 2, and Week 6
|
Cortical excitability will be evaluated by measuring motor evoked potential (MEP) amplitude. |
Baseline, Week 2, and Week 6
|
|
Change in Cortical Excitability Assessed by Motor Evoked Potential Latency
Time Frame: Baseline, Week 2, and Week 6
|
Cortical excitability will be evaluated by measuring motor evoked potential (MEP) latency. |
Baseline, Week 2, and Week 6
|
|
Change in Functional Ambulation Assessed by the Functional Ambulation Scale
Time Frame: Baseline, Week 2, and Week 6
|
Functional ambulation will be assessed using the Functional Ambulation Scale (FAS). The scale consists of six ordinal categories ranging from 0 to 5. A score of 0 indicates an inability to walk or the need for assistance from two or more people, whereas a score of 5 indicates independent walking on level and uneven surfaces, including stairs. Higher scores indicate greater independence in walking and a better functional outcome. |
Baseline, Week 2, and Week 6
|
|
Change in Independence in Activities of Daily Living Assessed by the Modified Barthel Index
Time Frame: Baseline, Week 2, and Week 6
|
Independence in activities of daily living and mobility will be assessed using the Modified Barthel Index. The index consists of 10 items, with item scores summed to yield a total score ranging from 0 to 100. A score of 0 indicates total dependence, whereas a score of 100 indicates independence in all assessed activities. Higher scores indicate greater functional independence and a better outcome. |
Baseline, Week 2, and Week 6
|
|
Change in Stroke-Specific Quality of Life
Time Frame: Baseline, Week 2, and Week 6
|
Stroke-specific quality of life will be assessed using the Turkish version of the Stroke-Specific Quality of Life Scale (SS-QOL). The scale consists of 48 items across eight domains. Each item is rated on a five-point scale ranging from 1 to 5. The mean item score will be calculated by averaging the scores of all 48 items, resulting in an overall score ranging from 1 to 5, with higher scores indicating better health-related quality of life. |
Baseline, Week 2, and Week 6
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Long H, Wang H, Zhao C, Duan Q, Feng F, Hui N, Mao L, Liu H, Mou X, Yuan H. Effects of combining high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke. Restor Neurol Neurosci. 2018;36(1):21-30. doi: 10.3233/RNN-170733.
- Kuzu O, Adiguzel E, Kesikburun S, Yasar E, Yilmaz B. The Effect of Sham Controlled Continuous Theta Burst Stimulation and Low Frequency Repetitive Transcranial Magnetic Stimulation on Upper Extremity Spasticity and Functional Recovery in Chronic Ischemic Stroke Patients. J Stroke Cerebrovasc Dis. 2021 Jul;30(7):105795. doi: 10.1016/j.jstrokecerebrovasdis.2021.105795. Epub 2021 Apr 20.
- Chen Q, Shen D, Sun H, Ke J, Wang H, Pan S, Liu H, Wang D, Su M, Fang Q. Effects of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation on motor recovery in patients following acute cerebral infarction. NeuroRehabilitation. 2021;48(1):83-96. doi: 10.3233/NRE-201606.
- Fu Y, Wang C, Zhang L, Ji D, Xiang A, Qi J, Zhao R, Wu L, Jin S, Zhang Q. The effectiveness of theta burst stimulation for motor recovery after stroke: a systematic review. Eur J Med Res. 2024 Nov 29;29(1):568. doi: 10.1186/s40001-024-02170-2.
- Meng Y, Zhang D, Hai H, Zhao YY, Ma YW. Efficacy of coupling intermittent theta-burst stimulation and 1 Hz repetitive transcranial magnetic stimulation to enhance upper limb motor recovery in subacute stroke patients: A randomized controlled trial. Restor Neurol Neurosci. 2020;38(1):109-118. doi: 10.3233/RNN-190953.
Study record dates
Study Major Dates
Study Start (Estimated)
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 (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AEŞH-2025-070
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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