Accelerated intermittent theta burst stimulation (iTBS) for the upper limb recovery after subacute stroke (ATLAS): study protocol for a multicenter randomized controlled trial.

Abstract

Background: Stroke is the second leading cause of death globally, with residual upper limb dysfunction being a major contributor to its high disability rate. Currently, there remains a lack of effective rehabilitation approaches to substantially improve upper limb dysfunction. While transcranial magnetic stimulation (TMS) has shown potential in promoting functional reorganization in stroke patients, more effective treatment protocols are still under exploration. In recent years, numerous clinical evidence has indicated that intermittent theta burst stimulation (iTBS) may offer a more efficient pathway for the upper limb recovery after stroke. A few studies have employed accelerated iTBS protocols, preliminarily confirming its safety and efficacy, yet large-sample comparative studies against the standard protocol are lacking. This ATLAS trial aims to compare the effects of accelerated iTBS versus a standard TMS protocol on upper limb recovery and overall functional outcomes in patients with subacute stroke.

Methods: This is a prospective, single-blind, multicenter, randomized controlled clinical trial. A total of 240 patients in the subacute phase of stroke will be recruited from 13 hospitals across 11 cities. Participants will be randomly allocated to either an iTBS group or a low-frequency repetitive TMS (LF-rTMS) group. Both groups will receive treatment 5 days per week for three consecutive weeks. In addition, all participants will receive standard conventional rehabilitation therapies, including physical agent modalities, therapeutic exercise, occupational therapy, and other commonly used clinical rehabilitation approaches. The primary outcome is the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) evaluated after 3 weeks of treatment. Secondary outcomes include measures of upper limb function, activities of daily living, clinical disease severity, and neurophysiological indicators assessed by rTMS, evaluated at both post-intervention and after a 3-week follow-up period.

Discussion: ATLAS trial is the first multicenter randomized controlled trial to apply an accelerated iTBS protocol to a large cohort of patients with subacute stroke and compare it directly with a standard stimulation protocol. The findings are expected to address the current gap in high-quality evidence regarding the efficacy of accelerated iTBS on upper limb recovery after stroke, thereby promoting the broader clinical adoption of more efficient iTBS-based therapeutic strategies.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2500110766). Registered on Oct 20, 2025.