Abstract
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive motor neuron degeneration, leading to severe functional decline and limited therapeutic options. While current pharmacological interventions such as Riluzole offer only modest benefits, there is a growing imperative to explore complementary rehabilitation strategies. Preclinical and neuroimaging evidence suggests that Tuina, a traditional Chinese manual therapy, may influence synaptic plasticity and integrity, offering a biologically reasonable mechanism for therapeutic benefit. METHODS: This randomized controlled trial, approved by the Ethics Committee of Hubei Provincial Hospital of Traditional Chinese Medicine (Approval No. HBZY2022-C42-01), will use a 1:1:1 allocation to enroll 135 participants. Participants will be assigned to: (i) Tuina therapy plus oral Riluzole, (ii) sham Tuina plus oral Riluzole, or (iii) Riluzole alone. Interventions will last for 1 year. The primary outcome is the change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Secondary outcomes include manual muscle test (MMT), modified Ashworth scale (MAS), forced vital capacity (FVC), vital capacity (VC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), maximal voluntary ventilation (MVV), and ALS Assessment Questionnaire (ALSAQ-40). Outcomes will be assessed at baseline, 4 weeks, and every 6 months up to 24 months. A mechanistic substudy will employ presynaptic Synaptic vesicle protein 2A (SV2A) PET imaging to quantify synaptic changes associated with Tuina intervention. DISCUSSION: This study is designed to evaluate the clinical efficacy of Tuina therapy combined with Riluzole and to investigate its potential to modulate synaptic integrity in patients with ALS. The findings are expected to provide evidence for integrating Tuina as an adjunctive, non-pharmacological therapy into comprehensive ALS management, linking functional improvements to underlying synaptic mechanisms. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn, identifier ChiCTR2300068650.