Clinical trial NCT07006571: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ALS
ALS (Amyotrophic Lateral Sclerosis)
Keywords: At-home tDCS
ALS
tDCS-ALS
Lead sponsor: University of Trieste
Sponsor class: OTHER
First posted: 2025-06-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Difference in the ALSFRS-R between groups at 16 weeks.
timeFrame: Baseline - 16 weeks
Secondary outcomes:
measure: Difference in the ALSFRS-R between groups at 32 weeks and 48 weeks
timeFrame: 32 weeks - 48 weeks
measure: Difference in the ALSAQ-40 between groups
timeFrame: Baseline - 16 weeks - 32 weeks - 48 weeks
measure: Difference in the Caregiver Burden Inventory (CBI) score between groups
timeFrame: Baseline - 16 weeks - 32 weeks - 48 weeks
measure: Difference in Quality of Life EQ-5D-5L Scale between groups
timeFrame: Baseline - 16 weeks - 32 weeks - 48 weeks
measure: Difference in Muscle strength assessed by manual dynamometer from baseline
timeFrame: Baseline - 16 weeks - 32 weeks - 48 weeks
measure: Difference in Plasma neurofilament levels between groups
timeFrame: Baseline - 16 weeks - 32 weeks - 48 weeks
measure: Difference in Survival from the onset of symptoms between groups
timeFrame: Continuously - 48 weeks
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: Clinica Neurologica, Azienda Sanitaria Universitaria Giuliano Isontina
Study officials:
affiliation: University of Trieste
name: Alberto Benussi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.