Clinical trial NCT03293394: Rehabilitative Trial With tDCS in Amyotrophic Lateral Sclerosis
Official title: Rehabilitative Trial With Transcranial Direct Current Stimulation (tDCS) in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Transcranial Direct Current Stimulation
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2017-09-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
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, the investigators will evaluate whether a two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with amyotrophic lateral sclerosis and 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.

In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with amyotrophic lateral sclerosis and modulate intracortical connectivity, at short and long term.

Subjects will be randomized in two groups, one receiving a 10 day (5 days/week for 2 weeks) treatment with anodal bilateral motor cortex tDCS and cathodal spinal tDCS and the other receiving sham stimulation with identical parameters. After the intervention, patients will be reassessed with a clinical and neurophysiological evaluation at 2 weeks, 2 months and 6 months after treatment. Furthermore, blood neurofilaments will be measured at each time point.

Clinical evaluation will include the ALSFRS-R, ALSAQ-40, CBI, EQ-5D-5L, muscle strength evaluated with the MRC scale.

Neurophysiological evaluation will include measures of intracortical connectivity, evaluated with transcranial magnetic stimulation (TMS) as short interval intracortical inhibition (SICI-ICF), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF).

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 months - 6 months
Secondary outcomes:
measure: Change in Short-interval Intracortical Inhibition (SICI) From Baseline
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change in the ALSFRS-R Score From Baseline
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change of Quality of Life From Baseline: ALSAQ-40 Scale
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change of Quality of Life From Baseline: EQ-5D-5L Scale
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change of Quality of Life From Baseline: EQ-VAS Scale
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change in Caregiver Burden (CBI)
timeFrame: Baseline - 2 weeks - 2 months - 6 months
measure: Change Intracortical Facilitation (ICF) From Baseline
timeFrame: Baseline - 2 weeks - 2 month - 6 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: AO Spedali Civili
state: BS
Study officials:
affiliation: Azienda Ospedaliera Spedali Civili, Brescia
name: Barbara Borroni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli Studi di Brescia
name: Alberto Benussi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quartarone A, Lang N, Rizzo V, Bagnato S, Morgante F, Sant'angelo A, Crupi D, Battaglia F, Messina C, Girlanda P. Motor cortex abnormalities in amyotrophic lateral sclerosis with transcranial direct-current stimulation. Muscle Nerve. 2007 May;35(5):620-4. doi: 10.1002/mus.20737.
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.