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

NCT ID: NCT06719947

Last Updated: 2025-07-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2027-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active HD-tDCS Group

Patients randomly included in this group will receive 10 sessions of anodal HD-tDCS stimulation. The intervention will take place at the participant's home, with electrodes positioned in a circular arrangement-one central electrode and four peripheral electrodes-over the cortical representation zone of the left primary diaphragmatic motor cortex, with a continuous current applied

Group Type: EXPERIMENTAL

Active HD-tDCS

Intervention Type: DEVICE

10 sessions of anodal HD-tDCS stimulation (neurostimulator coupled with a 4x1 HD-tDCS multichannel adapter) with a defined electrical current intensity over the cortical representation zone of the left diaphragmatic motor cortex

HD-tDCS sham group

Patients randomly included in this group will receive 10 sessions of sham HD-tDCS stimulation. The intervention will take place at the participant's home, with electrodes positioned in a circular arrangement-one central electrode and four peripheral electrodes-over the cortical representation zone of the left primary diaphragmatic motor cortex. Only an initial 30-second ramp stimulus will be applied, followed by a non-effective current

Group Type: PLACEBO_COMPARATOR

Simulated HD-tDCS

Intervention Type: DEVICE

10 sessions of sham anodal HD-tDCS stimulation (neurostimulator coupled with a 4x1 HD-tDCS multichannel adapter) over the cortical representation zone of the left diaphragmatic motor cortex. The device will provide a 30-second ramp and then maintain a minimal, non-effective continuous current

Interventions

Active HD-tDCS

10 sessions of anodal HD-tDCS stimulation (neurostimulator coupled with a 4x1 HD-tDCS multichannel adapter) with a defined electrical current intensity over the cortical representation zone of the left diaphragmatic motor cortex

Intervention Type: DEVICE

Simulated HD-tDCS

10 sessions of sham anodal HD-tDCS stimulation (neurostimulator coupled with a 4x1 HD-tDCS multichannel adapter) over the cortical representation zone of the left diaphragmatic motor cortex. The device will provide a 30-second ramp and then maintain a minimal, non-effective continuous current

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Financiadora de Estudos e Projetos

OTHER

Sponsor Role: collaborator

Universidade Federal do Rio Grande do Norte

OTHER

Sponsor Role: lead

Responsible Party

Guilherme Augusto de Freitas Fregonezi

Professor, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Universidade de Brasília - Campus Ceilândia

Brasília, Federal District, Brazil

PneumoCardioVascular Lab - HUOL/UFRN

Natal, Rio Grande do Norte, Brazil

Universidad Autónoma de Chile

Santiago, Santiago Metropolitan, Chile

Universidad do Chile

Santiago, Santiago Metropolitan, Chile

Countries

Brazil; Chile

Central Contacts

Guilherme A. F Fregonezi, PhD

Role: CONTACT

guilherme.fregonezi@ufrn.br

+55(84)99426-7896

Edna K. F Laurentino, MSc

Role: CONTACT

ednakarlaferreira@gmail.com

+55(84)99471-5172

Facility Contacts

Vinicius Z Maldaner da Silva, PhD

Role: primary

pneumocardiovascularlab@gmail.com

+55 61 99652-2517

Guilherme A. F Fregonezi, PhD

Role: primary

pneumocardiovascularlab@gmail.com

+55 84 3092-3624 ext. 3624

Edna K Ferreira Laurentino, MSc

Role: backup

ednakarlaferreira@gmail.com

+55 084 99471-5172

Matias Otto Yañez, PhD

Role: primary

matiasotto.kine@gmail.com

+56 9 8885-6626

Matias Otto Yañez, PhD

Role: backup

+56 9 8885-6626

Roberto Vera Uribe, MsC

Role: primary

robertovera@uchile.cl

Rodrigo Torres Castro, MsC

Role: backup

klgorodrigotorres@gmail.com

Other Identifiers

U1111-1306-808

Identifier Type: OTHER

Identifier Source: secondary_id

HD-tDCSALS

Identifier Type: -

Identifier Source: org_study_id