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

NCT06719947 | Not Yet Recruiting Phase 2

• 2 other identifiers: HD-tDCSALSU1111-1306-808
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 4

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Amyotrophic Lateral Sclerosis (ALS); Central Nervous System Diseases; Electric Stimulation Therapy; Transcranial Direct Current Stimulation

Outcome Measures

Primary Outcomes (3)

• Cortical excitability assessed via TMS

  Cortical excitability assessed by means of Transcranial Magnetic Stimulation measuring motor evoked potentials, cortical inhibition and duration of the cortical silent period

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Cortical tissue oxygenation

  Assessment of cortical tissue oxygenation using brain coupled near-infrared spectroscopy technique coupled to the brain to monitor cerebral oxygenation and regional cerebral oxygen saturation.

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Electromyographic activity of specific respiratory muscles

  This outcome will be assessed through Electromyography of the sternocleidomastoid, scalene, parasternal, hemidiaphragm and rectus abdominis muscles

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

Secondary Outcomes (11)

• Respiratory function assessed by spirometry

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Maximum Inspiratory and Expiratory Pressure

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Cough Peak Flow

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Respiratory muscle oxygenation via near-infrared spectroscopy

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

• Peripheral upper limb muscle activity assessed via electromyography

  From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up)

Study Arms (2)

Active HD-tDCS Group

EXPERIMENTAL

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

Device: Active HD-tDCS

HD-tDCS sham group

PLACEBO COMPARATOR

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

Device: Simulated HD-tDCS

Interventions

Active HD-tDCS 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

Active HD-tDCS Group

Simulated HD-tDCS 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

HD-tDCS sham group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidade Federal do Rio Grande do Norte: lead
• Financiadora de Estudos e Projetos: collaborator

Study Sites (4)

Universidade de Brasília - Campus Ceilândia

Brasília, Federal District, 72220-275, Brazil

Location

PneumoCardioVascular Lab - HUOL/UFRN

Natal, Rio Grande do Norte, 59010-090, Brazil

Location

Universidad Autónoma de Chile

Santiago, Santiago Metropolitan, 7500912, Chile

Location

Universidad do Chile

Santiago, Santiago Metropolitan, 8380453, Chile

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Guilherme A. F Fregonezi, PhD

CONTACT

+55(84)99426-7896; guilherme.fregonezi@ufrn.br

Edna K. F Laurentino, MSc

CONTACT

+55(84)99471-5172; ednakarlaferreira@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, PhD

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: November 30, 2024
• First Posted: December 6, 2024
• Study Start: August 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 2, 2025

Record last verified: 2025-07

Locations

CL (2); BR (2)