High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Therapy in Amyotrophic Lateral Sclerosis: Study Protocol for a Multicenter Randomized Controlled Clinical Trial.

Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron loss, muscle weakness, and respiratory dysfunction, often culminating in ventilatory failure. Evidence suggests that High-Definition Transcranial Direct Current Stimulation (HD-tDCS) may modulate motor cortical excitability and potentially influence motor and respiratory function in ALS. This study aims to evaluate the effects of home-based HD-tDCS applied over the primary diaphragmatic motor cortex on respiratory parameters and disease progression in individuals with ALS. Methods: This is a multicenter, randomized, controlled clinical trial. Eligible participants (aged 18-80, both sexes, diagnosed with ALS) will be randomized into an active HD-tDCS group (gTDCS) or a sham group (gSham). The intervention consists of 30 min daily HD-tDCS sessions (3 mA) applied for two weeks (5 days/week), using a 4 × 1 ring configuration targeting the diaphragmatic motor cortex. Sham stimulation includes an identical setup but only delivers ramp currents (30 s) with a minimal ongoing current (0.1 mA). Results: Pre-, intra-, and post-intervention evaluations will include measures of cortical excitability, cerebral and tissue perfusion, surface electromyography, respiratory and pulmonary function, fatigue, sleep quality, pain, motor performance, dyspnea, quality of life, and adverse effects. All procedures will be conducted at participants' homes with appropriate safety monitoring. Conclusions: This study will investigate the effects of HD-tDCS on respiratory and motor function in ALS and explore the feasibility of a home-based neuromodulation intervention. The outcomes may provide insight into non-pharmacological strategies for respiratory management in ALS.