Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase

Alberto Benussi; Valentina Cantoni; Mario Grassi; Ilenia Libri; Maria Sofia Cotelli; Barbara Tarantino; Abhishek Datta; Chris Thomas; Nadine Huber; Sari Kärkkäinen; Sanna-Kaisa Herukka; Annakaisa Haapasalo; Massimiliano Filosto; Alessandro Padovani; Barbara Borroni

doi:10.1016/j.brs.2023.11.008

Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase

Brain Stimul. 2023 Nov-Dec;16(6):1666-1676. doi: 10.1016/j.brs.2023.11.008. Epub 2023 Nov 15.

Authors

Affiliations

¹ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili di Brescia, Brescia, Italy.
² Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
³ Department of Brain and Behavioural Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, Italy.
⁴ Neurology Unit, Valle Camonica Hospital, Esine, Brescia, Italy.
⁵ Research & Development, Soterix Medical, Inc., New York, USA.
⁶ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
⁷ Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
⁸ Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
⁹ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; NeMo-Brescia Clinical Center for Neuromuscular Diseases, Gussago, Brescia, Italy.
¹⁰ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili di Brescia, Brescia, Italy. Electronic address: [email protected].

PMID: 37977335
DOI: 10.1016/j.brs.2023.11.008

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available.

Objective: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase.

Methods: Thirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates.

Results: Compared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival.

Conclusions: Cortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival.

Clinical trial registration: NCT04293484.

Keywords: Amyotrophic lateral sclerosis; Clinical trial; Motor neuron disease; Short interval intracortical inhibition; Transcranial direct current stimulation; Transcranial magnetic stimulation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis* / therapy
Double-Blind Method
Humans
Quality of Life
Transcranial Direct Current Stimulation*
Transcranial Magnetic Stimulation

Associated data

ClinicalTrials.gov/NCT04293484