Clinical trial NCT04293484: Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis
Official title: Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Motor Neuron Disease, Familial
Amyotrophic Lateral Sclerosis With Dementia
Keywords: Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Transcranial direct current stimulation
tDCS
Non-invasive brain stimulation
Transcranial magnetic stimulation
TMS
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2020-03-03
Enrollment: 31
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 motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Current drugs approved for ALS treatment only modestly slow disease progression.

Transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebral excitability in several neurodegenerative disorders and modulate intracortical connectivity measures.

In this randomized, double-blind, sham-controlled study followed by an open-label phase, the investigators will evaluate whether a repetition of two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS, after a six months interval, may further outlast clinical improvement in patients with amyotrophic lateral sclerosis and can modulate intracortical connectivity, at short and long term.

Detailed description: Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Current drugs approved for ALS treatment only modestly slow disease progression.

Transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebral excitability in several neurodegenerative disorders and modulate intracortical connectivity measures.

The present randomized, double-blind, sham-controlled study followed by an open-label phase will investigate a repetition of two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS, after a six months interval, may further outlast clinical improvement in patients with amyotrophic lateral sclerosis and modulate intracortical connectivity, at short and long term.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of probable, laboratory-supported probable, or definite amyotrophic lateral sclerosis according to the El Escorial revised criteria
* Disease duration ≤ 24 months
* Disease progression in the past 3 months
* Score ≥ 2 at the item "swallowing" of the ALS Functional Rating Scale Revised
* Score ≥ 2 at the item "walking" of the ALS Functional Rating Scale Revised
* Treatment with steady regimen of riluzole for a minimum of 1 month before study entry, and desiring its continuation
* Able to give informed consent
* Written informed consent

Exclusion Criteria:

* Motor neuron diseases other than ALS
* Severe head trauma in the past
* History of seizures
* History of ischemic stroke or hemorrhage
* Pacemaker
* Metal implants in the head/neck region
* Severe comorbidity
* Intake of illegal drugs
* Pregnancy

Primary outcomes:
measure: Change in Muscle Strength From Baseline
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Secondary outcomes:
measure: Change in Short-interval Intracortical Inhibition (SICI) From Baseline
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change in the ALSFRS-R Score From Baseline
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change of Quality of Life From Baseline: ALSAQ-40 Scale
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change of Quality of Life From Baseline: EQ-5D-5L Scale
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change of Quality of Life From Baseline: EQ-VAS Scale
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change in Caregiver Burden (CBI)
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
measure: Change Intracortical Facilitation (ICF) From Baseline
timeFrame: Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: AO Spedali Civili
state: BS
Study officials:
affiliation: Università degli Studi di Brescia
name: Barbara Borroni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli Studi di Brescia
name: Alberto Benussi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benussi A, Alberici A, Cotelli MS, Dell'Era V, Cantoni V, Bonetta E, Manenti R, Filosto M, Morini R, Datta A, Thomas C, Padovani A, Borroni B. Cortico-spinal tDCS in ALS: A randomized, double-blind, sham-controlled trial. Brain Stimul. 2019 Sep-Oct;12(5):1332-1334. doi: 10.1016/j.brs.2019.06.011. Epub 2019 Jun 8. No abstract available.
citation: Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.
citation: Menon P, Geevasinga N, Yiannikas C, Howells J, Kiernan MC, Vucic S. Sensitivity and specificity of threshold tracking transcranial magnetic stimulation for diagnosis of amyotrophic lateral sclerosis: a prospective study. Lancet Neurol. 2015 May;14(5):478-84. doi: 10.1016/S1474-4422(15)00014-9. Epub 2015 Apr 3.
citation: Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. Brain. 2011 Sep;134(Pt 9):2582-94. doi: 10.1093/brain/awr195. Epub 2011 Aug 11.