At-home Treatment With Cortico-spinal tDCS for Amyotrophic Lateral Sclerosis

Official title

Evaluation of the Efficacy of Home-based Transcranial Direct Current Stimulation on Physical Function in Patients With Amyotrophic Lateral Sclerosis: a Randomized, Controlled Clinical Trial

Overview

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that causes gradual muscle weakness and loss of muscle mass. It affects all muscles that control movement, speech, swallowing, and breathing. Unfortunately, ALS is currently incurable, and treatments are limited. Only two medications, riluzole and edaravone, have been approved and can slightly extend survival, typically between 20 and 48 months from diagnosis. Recent research has identified a useful biomarker known as neurofilament light chain (NfL), which increases in the blood as nerve cells become damaged. Measuring NfL levels can help track the progression of ALS. A promising non-invasive treatment called transcranial direct current stimulation (tDCS) has shown potential benefits for patients with ALS. tDCS involves safely applying mild electrical currents to specific areas of the brain and spinal cord. This approach aims to stimulate nerve cells, potentially improving their function and slowing disease progression. Initial studies have reported temporary improvements in muscle strength and survival when tDCS was used over a short period. Based on these encouraging results, our study proposes a new home-based tDCS treatment program specifically designed for ALS patients. Participants will use an easy-to-operate, safe, and portable device at home. The treatment involves placing electrodes on the scalp and the neck area to stimulate both the motor areas of the brain and the spinal cord. Therapy sessions will occur five days per week over 16 weeks. This home-based approach allows patients to comfortably receive therapy without daily trips to the hospital, making treatment more accessible and convenient. By providing this therapy at home, the investigators aim to improve the quality of life for ALS patients and explore new possibilities in treating and managing ALS and other neurodegenerative diseases.

Detailed description

Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disorder characterized by progressive muscle weakness and atrophy, affecting all skeletal and respiratory muscles. This leads to increasing difficulties in speech, swallowing, and ultimately breathing. A progressive rise in neurofilament light chain (NfL) levels-biomarkers of neuronal damage-has also been documented and may serve as a tool for monitoring disease progression. Average survival ranges from 20 to 48 months. Currently, there is no cure for ALS. Only two drugs, riluzole and edaravone, have demonstrated a modest extension of survival. In this context, transcranial direct current stimulation (tDCS) has emerged as a promising non-invasive neuromodulatory technique capable of modulating central nervous system excitability. Its popularity is growing due to its simplicity, low cost, and broad therapeutic potential across various neurodegenerative conditions. tDCS exerts long-lasting effects on synaptic plasticity in the motor cortex, primarily through modulation of NMDA receptors and GABAergic systems. Given that ALS involves irreversible degeneration of both upper and lower motor neurons in the motor cortex and spinal cord, tDCS may offer therapeutic benefit. Preliminary studies have shown transient improvements in muscle strength and survival following cortico-spinal tDCS administered over two weeks.

Building on these findings, a protocol is proposed for home-based tDCS treatment in ALS patients, consisting of multiple sessions aimed at achieving greater and more sustained effects. A brain stimulation device specifically designed for home use will be employed. This device incorporates safety features that monitor for improper usage.

The procedure involves applying an anodal stimulation over the motor cortex bilaterally and a cathodal stimulation over the cervical spinal cord. Stimulation sessions will be conducted five days per week over a 16-week period. Home-based tDCS offers a safe alternative to hospital-based treatment, eliminating the need for daily travel and allowing patients to undergo therapy in the comfort of their own homes. This approach represents a potentially significant innovation in ALS care-offering a non-invasive, safe, and accessible therapeutic option that may enhance quality of life and open new avenues for research in neurodegenerative disease management.

Interventions

• Device Real tDCS
  The electrodes of the device will be positioned according to the following scheme: one electrode (anode) will be applied on the skin overlying the motor cortices, one electrode (cathode) will be applied on the skin overlying the cervical cord, in the area corresponding to C6. Dosage: 4 mA for the anodal electrode and 4 mA for the cathodal electrode (intensity could be reduced if not tollerate by the patient). Duration of stimulation: 20 minutes per session. Frequency: 5 days per week (Monday - F
• Device Sham tDCS
  The electrodes will be positioned in the same way as the active device, but the current flow will be limited to the ramp-up (start of stimulation) and ramp-down (end of stimulation) phase, mimicking the sensation of stimulation without providing actual treatment. Dosage: Simulation of stimulation without actual current. Duration of stimulation: 20 minutes per session. Frequency: 5 days per week (Monday - Friday) for 16 weeks.

Primary outcome measures

• Difference in the ALSFRS-R between groups at 16 weeks. [Time frame: Baseline - 16 weeks]

Secondary outcome measures (7)

• Difference in the ALSFRS-R between groups at 32 weeks and 48 weeks [Time frame: 32 weeks - 48 weeks]
• Difference in the ALSAQ-40 between groups [Time frame: Baseline - 16 weeks - 32 weeks - 48 weeks]
• Difference in the Caregiver Burden Inventory (CBI) score between groups [Time frame: Baseline - 16 weeks - 32 weeks - 48 weeks]
• Difference in Quality of Life EQ-5D-5L Scale between groups [Time frame: Baseline - 16 weeks - 32 weeks - 48 weeks]
• Difference in Muscle strength assessed by manual dynamometer from baseline [Time frame: Baseline - 16 weeks - 32 weeks - 48 weeks]
• Difference in Plasma neurofilament levels between groups [Time frame: Baseline - 16 weeks - 32 weeks - 48 weeks]
• Difference in Survival from the onset of symptoms between groups [Time frame: Continuously - 48 weeks]

Eligibility criteria

Inclusion criteria

• Male or female patients with a probable, laboratory-supported diagnosis of ALS, or defined ALS according to current clinical criteria
• Age greater than 18 years
• Onset of disease ≤ 24 months
• Disease progression in the last 3 months
• A score ≥ 2 on the "respiratory failure" item on the ALS Functional Rating Scale Revised (ALSFRS-R)
• Treatment with riluzole or edaravone is permitted, provided it has been stable for at least 1 month prior to enrollment in the study, or no ALS-specific treatment
• Presence of a caregiver who can assist the patient and who has successfully completed the necessary training in the use of the device
• Signature of informed consent

Exclusion criteria

• People with fixed electrical stimulators (e.g. cardiac pacemakers, nerve stimulators, hearing implants) that would not work or would be damaged by the electric field;
• People with particular intracranial metal foreign bodies (e.g. splinters, some prostheses, screws and nails) that could interact with the electric field
• People with a history of epilepsy;
• As the effects of tDCS on the developing fetus are not known, pregnant women will be excluded from the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Clinica Neurologica, Azienda Sanitaria Universitaria Giuliano Isontina — Trieste

Publications

• Benussi A, Di Lorenzo F, Dell'Era V, Cosseddu M, Alberici A, Caratozzolo S, Cotelli MS, Micheli A, Rozzini L, Depari A, Flammini A, Ponzo V, Martorana A, Caltagirone C, Padovani A, Koch G, Borroni B. Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia. Neurology. 2017 Aug 15;89(7):665-672. doi: 10.1212/WNL.0000000000004232. Epub 2017 Jul 26. PMID 28747446
• Benussi A, Koch G, Cotelli M, Padovani A, Borroni B. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study. Mov Disord. 2015 Oct;30(12):1701-5. doi: 10.1002/mds.26356. Epub 2015 Aug 14. PMID 26274840

Identifiers

NCT: NCT07006571 · 371/2024H

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗