Individualized rTMS Synchronized Task Training for Closed-loop Neuromodulation of Post-stroke Motor Dysfunction

Official title

Individualized Closed-Loop Neuromodulation With Repetitive Transcranial Magnetic Stimulation Synchronized Task Training for Upper Limb Motor Dysfunction in Stroke Patients

Overview

The goal of this clinical trials is to investigate the effectiveness of individualized 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 individualized rTMS precise target combined with motor training improve upper limb motor rehabilitation in patients？ 2. Does individualized rTMS precise target 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 individualized online rTMS to non-individualized online and individualized sham stimulation in stroke patients to see if individualized online rTMS works to alleviate motor dysfunction in this randomized，sham-controlled, double-blind trial. Participants will: 1. randomized to one group(individualized online, non-individualized online 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.

Interventions

• Device Individualized online stimulation
  The individualized online stimulation group will calculate precise targets based on the collected multimodal MRI (structural images, resting-state/task-state functional images, and diffusion tensor imaging), plan the coil position and placement angle of TMS through electric field simulation, and achieve individualized intervention. At the same time, when patients receive TMS treatment, they are matched with specific upper limb motor tasks. When the task starts autonomously, TMS stimulation is tr
• Device Non-individualized online stimulation
  In the non-individualized online stimulation group, patients receive TMS treatment synchronized with task training. However, the targeting uses traditional positioning methods, i.e., determining the target with a positioning cap instead of precise target localization.
• Device Sham stimulation
  In the individualized online sham stimulation group, patients receive TMS treatment combined with specific tasks. The stimulation targets are the same as those in the online stimulation group, all determined by precise target localization, except that a sham stimulation coil is used for TMS stimulation.

Primary outcome measures

• Fugl-Meyer Assessment - Upper Extremity (FMA-UE) [Time frame: Baseline; Day 1 After 2-week intervention; Day 30 after 2-week intervention; Day 90 after 2-week intervention]

Secondary outcome measures (5)

• Action Research Arm Test (ARAT) [Time frame: Baseline; Day 1 After 2-week intervention; Day 30 after 2-week intervention; Day 90 after 2-week intervention]
• Modified Barthel Index (MBI) [Time frame: Baseline; Day 1 After 2-week intervention; Day 30 after 2-week intervention; Day 90 after 2-week intervention]
• The Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline; Day 1 After 2-week intervention; Day 30 after 2-week intervention; Day 90 after 2-week intervention]
• Motor Evoked Potential (MEP) - Resting Motor Threshold (RMT) [Time frame: Baseline; Day 6 during 2-week intervention; Day 1 After 2-week intervention; Day 30 after 2-week intervention; Day 90 after 2-week intervention]
• The average completion time for baseline tasks [Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day7, Day 8, Day 9, Day 10 during TMS intervention]

Eligibility criteria

Inclusion criteria

• The patient is first diagnosed with stroke through neurological examination, CT or MRI scan.
• The vital signs are stable and there is a certain degree of upper limb motor dysfunction.
• Motor evoked potentials(MEPs) of First Dorsal Interosseous Muscle（FDI）or Abductor Pollicis Brevis Muscle (APB) is negative in ipsilesional hemisphere.
• The age is between 20 and 80 years old.
• The cognitive ability is not significantly affected and the patient can cooperate with various examinations and assessments, with a MMSE score ≥ 20 points.
• There are no serious complications (such as pneumonia, heart failure, urinary tract infection or malnutrition).
• 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).
• The patient or guardian agrees to sign the informed consent form.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Ruijin Hospital, affiliated to Shanghai Jiao Tong University, School of medicine — Shanghai

Publications

• Khedr EM, Etraby AE, Hemeda M, Nasef AM, Razek AA. Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke. Acta Neurol Scand. 2010 Jan;121(1):30-7. doi: 10.1111/j.1600-0404.2009.01195.x. Epub 2009 Aug 11. PMID 19678808
• Ackerley SJ, Stinear CM, Barber PA, Byblow WD. Combining theta burst stimulation with training after subcortical stroke. Stroke. 2010 Jul;41(7):1568-72. doi: 10.1161/STROKEAHA.110.583278. Epub 2010 May 20. PMID 20489170
• Xiang H, Sun J, Tang X, Zeng K, Wu X. The effect and optimal parameters of repetitive transcranial magnetic stimulation on motor recovery in stroke patients: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2019 May;33(5):847-864. doi: 10.1177/0269215519829897. Epub 2019 Feb 18. PMID 30773896
• Zhang L, Xing G, Fan Y, Guo Z, Chen H, Mu Q. Short- and Long-term Effects of Repetitive Transcranial Magnetic Stimulation on Upper Limb Motor Function after Stroke: a Systematic Review and Meta-Analysis. Clin Rehabil. 2017 Sep;31(9):1137-1153. doi: 10.1177/0269215517692386. Epub 2017 Feb 17. PMID 28786336
• van Lieshout ECC, van der Worp HB, Visser-Meily JMA, Dijkhuizen RM. Timing of Repetitive Transcranial Magnetic Stimulation Onset for Upper Limb Function After Stroke: A Systematic Review and Meta-Analysis. Front Neurol. 2019 Dec 3;10:1269. doi: 10.3389/fneur.2019.01269. eCollection 2019. PMID 31849827
• Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3. PMID 26850210
• Kim JH. Effects of a virtual reality video game exercise program on upper extremity function and daily living activities in stroke patients. J Phys Ther Sci. 2018 Dec;30(12):1408-1411. doi: 10.1589/jpts.30.1408. Epub 2018 Nov 21. PMID 30568325
• Diekhoff-Krebs S, Pool EM, Sarfeld AS, Rehme AK, Eickhoff SB, Fink GR, Grefkes C. Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients. Neuroimage Clin. 2017 Jun 4;15:559-571. doi: 10.1016/j.nicl.2017.06.006. eCollection 2017. PMID 28652969

Identifiers

NCT: NCT07049211 · 2025296

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗