rTMS Combined With Motor Training for the Treatment of Upper Limb Motor Dysfunction in Stroke Patients (rTMS)

The goal of this clinical trials is to investigate the effectiveness of online repetitive transcranial magnetic stimulation (rTMS) in enhancing upper limb motor rehabilitation during the subacute and chronic phase of stroke. It will also learn about the safety of online rTMS intervention methods. The main questions it aims to answer are:

1. Does rTMS combined with motor training improve motor rehabilitation in patients？
2. Does repetitive transcranial magnetic stimulation (rTMS) combined with motor training enhance the upper limb motor rehabilitation ability in stroke patients by strengthening the functional coupling of the motor circuit to achieve functional reorganization of the brain network ?

Researchers will compare online rTMS to offline and sham stimulation in stroke patients to see if online rTMS works to alleviate motor dysfunction in multicenter multicenter, blinded and controlled trial.

Participants will:

1. randomized to one group(online, offline or sham);
2. receive rTMS treatment for 10 days, with 5 working days per week for a total of two weeks;
3. receive magnetic resonance imaging (MRI) and electroencephalogram (EEG) evaluations before and after the entire treatment;
4. conduct scales and MEP assessment one day before the treatment, as well as one day, one month, and three months after the treatment.

Study Overview

• Status: Completed
• Conditions: Stroke; Upper Extremity Paresis
• Intervention / Treatment: Device: Online stimulation; Device: Offline stimulation; Device: Sham stimulation

Detailed Description

In this study, patients were be randomly assigned to three groups: online, offline and sham groups. if patients were able to induce MEPs, intensity of TMS will be 80% RMT; if not , inensity of TMS will be 70%~80% of TMS output.

Patients were stimulated over 2 week period, 4 sessions of tasks were performed everyday. The patient will undergo a 2-week (10-day) stimulation protocol, with fourty tasks performed daily. This includes one session of 10 baseline tasks measurement and three sessions of 5 Hz rTMS synchronized with 10 motor tasks. rTMS will be applied to the ipsilesional motor cortex.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Shanghai Ruijin Hospital, affiliated to Shanghai Jiao Tong University, School of medicine
  • Songjiang
    • Shanghai, Songjiang, China
      • Shanghai Yang Zhi Rehabilitation Hospital
  • Yangpu
    • Shanghai, Yangpu, China
      • Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient is first diagnosed with stroke through neurological examination, CT or MRI scan.
2. The vital signs are stable and there is a certain degree of upper limb motor dysfunction.
3. The age is between 20 and 80 years old.
4. The cognitive ability is not significantly affected and the patient can cooperate with various examinations and assessments, with a MMSE score ≥ 20 points.
5. There are no serious complications (such as pneumonia, heart failure, urinary tract infection or malnutrition).
6. There is no pathological condition that is a contraindication for TMS in the medical history (for example, patients with metal in the brain, such as aneurysm clips, patients with a cardiac pacemaker, pregnant women, or those with a history of epileptic seizures).
7. The patient or guardian agrees to sign the informed consent form.

Exclusion Criteria:

1. Patients with severe heart, lung, liver, kidney diseases and malignant tumors;
2. Those with a history of aphasia, severe cognitive impairment or mental illness;
3. Patients who have had a history of epileptic seizures in the last month or are taking anti-epileptic drugs recently;
4. Those with severe visual or hearing impairments, unable to communicate normally;
5. People with metal implants, pacemakers, skull defects or other conditions that prevent them from undergoing TMS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Online stimulation; 5 Hz rTMS is applied to the primary motor cortex on the affected hemisphere when the patients are performing motor tasks.	Device: Online stimulation; 5 Hz rTMS is applied to the primary motor cortex on the affected hemisphere when the patients are performing motor tasks.
Active Comparator: Offline stimulation; After 5 Hz rTMS is applied to the primary motor cortex on the affected hemisphere, the patients perform motor tasks.	Device: Offline stimulation; After 5 Hz rTMS is applied to the primary motor cortex on the affected hemisphere, the patients perform motor tasks.
Sham Comparator: Sham stimulation; Sham rTMS is applied to the primary motor cortex on the affected hemisphere when the patients are performing motor tasks.	Device: Sham stimulation; Sham rTMS is applied to the primary motor cortex on the affected hemisphere when the patients are performing motor tasks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in FM-UE From Baseline	The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. It is applied clinically and in research to determine disease severity, describe motor recovery, and to plan and assess treatment. The Fugl-Meyer Assessment - Upper Extremity (FMA-UE) is the upper limb motor domain includes items assessing movement, coordination, and reflex action of the shoulder, elbow, forearm, wrist, hand. It ranges from 0 (hemiplegia) to 66 points (normal motor performance). FM-UE scale was assessed by site raters who were masked to the intervention).	Before intervention (day0); After intervention (day15); Follow-up 1 (day45); Follow-up 2 (day105)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The average completion time for baseline tasks	The average completion time for baseline tasks refers to the time (seconds) taken by the patient to complete the baseline motor task before each intervention.	Before intervention (Week 0); Middle of intervention (Week 1); After intervention (Week 2)
Mean Change in ARAT score from Baseline	The Action Research Arm Test (ARAT) is a 19 item observational measure used by physical therapists and other health care professionals to assess upper extremity performance (coordination, dexterity and functioning) in stroke recovery, brain injury and multiple sclerosis populations. The ARAT was originally described by Lyle in 1981 as a modified version of the Upper Extremity Function Test and was used to examine upper limb functional recovery post damage to the cortex. ARAT score was assessed by site raters who were masked to the intervention.	Before intervention (day0); After intervention (day15); Follow-up 1 (day45); Follow-up 2 (day105)
Mean Change in WMFT score from Baseline	The WMFT is used to assess the upper limb motor function of patients and serves as an effective supplement to the FMA-UE. By timing single-joint movements, multi-joint movements, and functional activities, as well as evaluating movement quality and speed, it can quantitatively assess the upper limb motor ability of stroke patients. It is more sensitive to patients with mild to moderate stroke, and its grading is relatively detailed, which can sensitively reflect the subtle changes in patients' motor function during evaluation. The WMFT consists of 15 items, among which items 1-6 are simple joint movements, and items 7-15 are complex functional actions. This scale can not only evaluate impairments but also assess the effect of training on disabilities. The WMFT has good validity and reliability and can be used to evaluate the upper limb function of stroke patients. WMFT score was assessed by site raters who were masked to the intervention.	Before intervention (day0); After intervention (day15); Follow-up 1 (day45); Follow-up 2 (day105)
Mean Change in MBI score from Baseline	The Barthel Index for activities of daily living was introduced in 1965 by Barthel and Mahoney to be used in the assessment of the degree of assistance required by patients with stroke (other neuromuscular or musculoskeletal disorders or oncology patients) with regards to 10 items of mobility and self-care (ADL). MBI score was assessed by site raters who were masked to the intervention.	Before intervention (day0); After intervention (day15); Follow-up 1 (day45); Follow-up 2 (day105)
Mean Change in PSQI score from Baseline	The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire that assesses sleep quality over a one-month time interval. The PSQI is commonly used in both clinical and research settings to evaluate various aspects of sleep. It is a valuable tool for assessing sleep quality as it captures multiple dimensions of sleep, including both subjective experiences and objective parameters. It allows researchers and healthcare providers alike to obtain a comprehensive understanding of an individual's sleep patterns and disturbances and inform treatment decisions and interventions for sleep disorders. PSQI score was assessed by site raters who were masked to the intervention).	Before intervention (day0); After intervention (day15); Follow-up 1 (day45); Follow-up 2 (day105)
Motor Evoked Potential (MEP) - Resting Motor Threshold (RMT)	Resting motor threshold is an objective measure of cortical excitability. Numerous studies indicate that the success of motor recovery after stroke is significantly determined by the direction and extent of cortical excitability changes.	Before intervention (day 0); In the middle of intervention (day 6); After intervention (day15); Follow-up 1 (day 45); Follow-up 2 (day105)
MRI changes	multi-modal MRI scanned, including structural MRI, resting-fMRI, task-fMRI, and DTI	Before intervention (day 0); After intervention (day15)
Adverse events	adverse events such as headache, sleep disturbance, etc	Before intervention (day 0); In the middle of intervention (day 6); After intervention (day15)

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Changhai Hospital; shanghai center for brain science and brain-inspired technology; Shanghai Sunshine Rehabilitation Center

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Actual): September 10, 2025
• Study Completion (Actual): September 10, 2025

Study Registration Dates

• First Submitted: December 27, 2024
• First Submitted That Met QC Criteria: December 27, 2024
• First Posted (Actual): December 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Repetitive Transcranial Magnetic Stimulation; online; Motor evoked potentials; individualized; Upper Limb Motor Dysfunction; motor task training
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Paresis
• Other Study ID Numbers: 2022361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study plans to share individual participant data with qualified researchers under specific conditions. Please refer to https://zenodo.org/records/17345584
• IPD Sharing Time Frame: Starting 6 months after publication

IPD Sharing Access Criteria

Authorized professional researchers, including but not limited to researchers engaged in neuroscience research who have obtained data access permission from their affiliated institutions, and clinical doctors from other medical institutions that have a cooperative relationship with this study and have signed data confidentiality agreements.

They can access the detailed clinical medical histories of the participants, including past disease histories and treatment process records; neurological function assessment scale data; as well as imaging data collected during the study, such as brain magnetic resonance imaging (MRI) results. However, sensitive information related to participants' privacy, such as names, ID numbers, and contact information, will be strictly anonymized to ensure that such information cannot be obtained.

They can contact the corresponding author or the first author via email.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No