Abstract
<title>Abstract</title> <p>Background Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. Preliminary clinical evidence suggests that electroacupuncture (EA) may benefit AIS recovery, and preclinical studies have demonstrated neuroprotective, anti-apoptotic and anti-inflammatory effects of EA in ischemic stroke models; however, high-quality clinical evidence from rigorously controlled trials remains scarce, and the underlying central mechanisms are largely unknown. This trial aims to evaluate the efficacy and safety of EA for AIS and to explore its central neurological mechanisms using multimodal magnetic resonance imaging (MRI). Methods This is a single-centre, randomized, sham-controlled, patient- and assessor-blinded, parallel-group superiority trial with an embedded multimodal neuroimaging substudy. A total of 84 eligible AIS patients who also meet the diagnostic criteria for the traditional Chinese medicine (TCM) “stasis-toxin interlocking” syndrome will be randomly allocated (1:1) to an EA group or a sham-control group, stratified by eligibility for the MRI substudy. All participants will receive standard medical care plus 10 treatment sessions over 2 weeks. The primary outcome is the change in the National Institutes of Health Stroke Scale (NIHSS) score from baseline (Day 1) to Day 14. Secondary outcomes include the Fugl-Meyer Assessment (FMA), modified Rankin Scale (mRS), modified Barthel Index (MBI), Activities of Daily Living (ADL) scale, and a TCM symptom observation score, assessed at Days 1, 7 and 14; clinical endpoint events (stroke recurrence, deterioration and death) will be recorded. In the substudy (n = 60), multimodal MRI (3D-T1, resting-state functional MRI, susceptibility-weighted imaging and diffusion-weighted imaging) will be performed at Days 1 and 14, and blood samples will be retained for future mechanistic analyses. Imaging parameters will be correlated with clinical outcomes to investigate potential central mechanisms. Discussion By combining a validated sham-controlled, patient-blinded design with longitudinal multimodal MRI, this trial will provide rigorous clinical evidence for EA in AIS and objective neuroimaging insights into its mechanisms. Key limitations include the inherent risk of practitioner unblinding, the single-centre design with a modest sample size, and the absence of long-term follow-up. Trial registration: International Traditional Medicine Clinical Trial Registry (ITMCTR), a World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) primary registry, ITMCTR2024000876. Registered prospectively on 11 November 2024, before enrolment of the first participant. https://itmctr.ccebtcm.org.cn</p>