Exploration of neuroimmune and brain network mechanisms of Jin’s three-needle therapy in promoting ischemic stroke recovery: a randomized controlled trial protocol

Background Functional impairment during the recovery phase of ischemic stroke (IS) substantially diminishes patients’ long-term quality of life. Although rehabilitation therapy promotes functional recovery, some patients still face persistent functional limitations, underscoring the need for effective adjuvant interventions. Acupuncture is widely used in stroke rehabilitation, and Jin’s three-needle therapy has shown potential benefits for post-stroke motor dysfunction. However, high-quality randomized controlled trial evidence regarding its clinical efficacy and neuroimmunomodulatory mechanisms remains limited. Objective This study aims to evaluate the clinical efficacy of Jin’s three-needle therapy for functional impairment during the recovery phase of ischemic stroke, and to explore potential associations between brain functional network changes and peripheral immune alterations using resting-state functional magnetic resonance imaging (rs-fMRI) and immune marker assessments. Methods This randomized, controlled, assessor-blinded trial will enroll 70 patients with ischemic stroke in the recovery phase from The First Affiliated Hospital of Guangzhou University of Chinese Medicine. Participants will be randomly assigned to receive either Jin’s three-needle therapy or non-penetrating sham acupuncture, while both groups receive the same standardized conventional rehabilitation and guideline-based basic treatment. The intervention will be administered for 3 weeks (5 treatment days per week). Treatment providers will not be blinded, whereas patients, outcome assessors, and data analysts will remain blinded. The primary outcome is the change in the National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes include the Modified Barthel Index (MBI) and modified Rankin Scale (mRS). Exploratory outcomes include peripheral immune-related markers, including regulatory T cell proportion, CD39 expression on Tregs, plasma plasminogen activator inhibitor-1 (PAI-1) levels, and rs-fMRI-based functional connectivity changes. Associations among changes in clinical outcomes, brain functional connectivity, and peripheral biomarkers will be explored. Follow-up assessments will be conducted at 1 and 3 months after discharge. Discussion This study integrates clinical assessments, peripheral biomarker measurements, and brain functional imaging to investigate the multidimensional effects of Jin’s three-needle therapy on functional impairment during the recovery phase of ischemic stroke. The findings may provide objective evidence for evaluating this therapy and characterize treatment-associated changes in peripheral immune-related biomarkers and brain functional connectivity, as well as their associations with clinical recovery. Clinical trial registration https://itmctr.ccebtcm.org.cn/mgt/search , identifier ITMCTR2026001598.