Advantage of cerebellar intermittent theta-burst stimulation in Alzheimer's disease (ACT-AD): study protocol for a multicenter, randomized, double-blind, sham-controlled trial

Abstract

The cerebellum plays a crucial role in cognitive processing and thus presents a promising therapeutic target for Alzheimer’s disease (AD). This trial aims to evaluate the efficacy and safety of long-term, neuronavigated cerebellar intermittent theta burst stimulation (iTBS) in patients with AD. The ACT-AD trial is a multicenter, randomized, double-blind, sham-controlled study involving 100 participants with mild-to-moderate AD across 4 centers in China. Participants will be randomized to receive either cerebellar iTBS or sham stimulation for 4 weeks (daily sessions), followed by 8 weeks of weekly maintenance sessions. The primary outcome is the change in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score from baseline to week 12. Secondary outcomes include additional clinical scales. Exploratory outcomes include electroencephalogram (EEG), blood biomarkers and magnetic resonance imaging (MRI). Statistical analysis will follow intention-to-treat principles using mixed models for repeated measures (MMRM). The ACT-AD trial will assess the efficacy and safety of long-term, neuronavigated cerebellar iTBS in treating patients with mild-to-moderate AD. ClinicalTrials.gov, NCT06669182. Registered on 31 October 2024.