HD-tDCS in Amyotrophic Lateral Sclerosis: A Multicenter Randomized Controlled Trial

High-Definition Transcranial Direct Current Stimulation (HD-tDCS) in Amyotrophic Lateral Sclerosis: A Multicenter Randomized Controlled Trial

Amyotrophic Lateral Sclerosis (ALS) is a nervous system disease that causes muscle weakness and rapidly progresses to the loss of mobility and functionality. Studies suggest that High-Definition Transcranial Direct Current Stimulation (HD-tDCS) is a technique for modulating motor cortical hyperexcitability. However, evidence on the use of HD-tDCS as a neuromodulator of the diaphragmatic motor cortex in people with ALS is inconclusive.

A multicenter, randomized controlled clinical trial will be conducted. Participants will be randomized into two groups: the HD-tDCS group (gTDCS) and the sham tDCS group (gSham). The intervention protocol will assess the effects of HD-tDCS on respiratory parameters and ALS progression. The study will include individuals of both sexes, aged 18 to 80 years, with a clinical diagnosis of ALS, evaluated before, during, and after the home-based HD-tDCS protocol. The electrodes will be positioned in a circular arrangement over the primary diaphragmatic motor cortex, applying a continuous anodal current intensity. For placebo comparison, only an initial 30-second ramp stimulus will be applied, followed by a minimal current, resulting in no significant intervention. The intervention will be conducted at the participant's home, once daily, five days per week, for two weeks. Patients will undergo evaluations of lung function, cough peak flow, respiratory muscle strength, nasal respiratory pressures, functional capacity, muscle fatigue, cognitive function, as well as surface electromyography of respiratory muscles during active and assisted breathing curves using transcranial magnetic stimulation (TMS), cortical excitability, central tissue oxygenation, respiratory muscle tissue oxygenation, functionality and disease progression, motor control and muscle performance, fatigue and dyspnea, sleep analysis, quality of life, and adverse effects.

Inclusion Criteria:

• Both sexes; diagnosis of ALS according to the revised El Escorial criteria;
• Age between 18 and 80 years;
• Forced Vital Capacity greater than 50% of predicted;
• Sniff nasal inspiratory pressure greater than 40 cmH2O;
• A telephone number to contact the care team and who signed the study consent form.

Exclusion Criteria:

• Subjects who are unable to understand or perform any of the study procedures;
• Subjects who do not agree to participate or voluntarily request withdrawal from the study at any time;
• Subjects with cardiac, respiratory, or musculoskeletal comorbidities;
• Subjects using invasive mechanical ventilation;
• Subjects with a tracheostomy;
• Subjects with a pacemaker;
• Subjects with metallic brain implants or other electronic implants;
• Subjects with a cochlear implant;
• Subjects with epileptic activity or a history of epilepsy, or a family history of epilepsy;
• Subjects with a history of stroke or tumor;
• Subjects prone to severe hemodynamic fluctuations, acute infectious processes, and/or inflammatory conditions;
• Pregnant women at the time of recruitment;
• Subjects who are unable to complete the intervention protocol.