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Clinical Trials/NCT06719947
NCT06719947
Not yet recruiting
Phase 2

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

Universidade Federal do Rio Grande do Norte4 sites in 2 countries80 target enrollmentAugust 1, 2025

Overview

Phase
Phase 2
Intervention
Not specified
Conditions
Amyotrophic Lateral Sclerosis (ALS)
Sponsor
Universidade Federal do Rio Grande do Norte
Enrollment
80
Locations
4
Primary Endpoint
Cortical excitability assessed via TMS
Status
Not yet recruiting
Last Updated
10 months ago

Overview

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.

Registry
clinicaltrials.gov
Start Date
August 1, 2025
End Date
December 1, 2027
Last Updated
10 months ago
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Guilherme Augusto de Freitas Fregonezi

Professor, PhD

Universidade Federal do Rio Grande do Norte

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;

Outcomes

Primary Outcomes

Cortical excitability assessed via TMS

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

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

Cortical tissue oxygenation

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

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.

Electromyographic activity of specific respiratory muscles

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

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

Secondary Outcomes

  • 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))
  • Functionality and disease progression(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))
  • Fatigue Severity(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))
  • Dyspnea assessed via Modified Borg Scales(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))
  • Quality of sleep assessment(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))
  • Quality of life assessed using the Brief ALS-specific Quality of Life Questionnaire(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))
  • Subjective assessment of stimulation-related effects(From the date of randomization (1 week before the start of the intervention) up to 6 months (follow-up))

Study Sites (4)

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