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Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis

Not Applicable
Completed
Conditions
Motor Neuron Disease, Familial
Amyotrophic Lateral Sclerosis With Dementia
Interventions
Device: Anodal bilateral motor cortex and cathodal spinal tDCS
Device: Sham bilateral motor cortex and sham spinal tDCS
Registration Number
NCT04293484
Lead Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sham tDCS - Real tDCSSham bilateral motor cortex and sham spinal tDCS10 sessions of sham bilateral motor cortex and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)
Real tDCS - Real tDCSAnodal bilateral motor cortex and cathodal spinal tDCS10 sessions of anodal bilateral motor cortex and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)
Sham tDCS - Real tDCSAnodal bilateral motor cortex and cathodal spinal tDCS10 sessions of sham bilateral motor cortex and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)
Primary Outcome Measures
NameTimeMethod
Change in Muscle Strength From BaselineBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

A megascore is obtained by summing scores of single muscles (shoulder abductors, elbow flexors and extensors, wrist flexors, thumb opponent, hip flexors, knee flexors and extensors, and ankle dorsiflexors and extensors on both sides) manually evaluated according to the Medical Research Council (MRC) scale, which ranges from 0 (no movement) to 5 (normal contraction).

The score for each muscle is summed, with scores ranging from 100 (no impairment) to 0 (most severe impairment).

Secondary Outcome Measures
NameTimeMethod
Change in Caregiver Burden (CBI)Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Change of quality of life from baseline evaluated with the CBI scale. The CBI scale is 24- item scale designed to assess the experience of caregivers of older people. The multidimensional instrument assesses five domains of burden (time-dependence, developmental, physical, social, and emotional). Items are scored on a 4-point scale, ranging from "not at all descriptive" to "very descriptive". The scale ranges from 0 (no impairment) to 96 (severe impairment).

Change of Quality of Life From Baseline: ALSAQ-40 ScaleBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Change of quality of life from baseline evaluated with the ALSAQ-40 scale. The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ) is a patient self-report health status scale. The ALSAQ is specifically used to measure the subjective well-being of patients with amyotrophic lateral sclerosis. There are 40 items/questions with 5 discrete scales: physical mobility (10 items), activities of daily living and independence (10 items), eating and drinking (3 items), communication (7 items), emotional reactions (10 items). Patients are asked to think about the difficulties they may have experienced during the last two weeks (e.g. I have found it difficult to feed myself). Patients are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale):

never/rarely/sometimes/often/always or cannot do at all. The total ranges from 0 (no impairment) to 160 (severe impairment).

Change of Quality of Life From Baseline: EQ-VAS ScaleBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Change of quality of life from baseline evaluated with the EQ-VAS scale. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. The scale ranges from 0 (severe impairment) to 100 (no impairment).

Change in Short-interval Intracortical Inhibition (SICI) From BaselineBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on short-interval intracortical inhibition (SICI) from baseline

Change in the ALSFRS-R Score From BaselineBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Change in the ALS Functional Rating Scale (ALSFRS-R) score from baseline. The ALSFRS provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALSFRS includes ten questions that rate the patients level of functional impairment in performing one of ten common tasks. Each task is rated on a five-point scale from 0 (can't do) to 4 (normal ability). Individual item scores are summed to produce a reported score of between 40 (no impairment) and 0 (severe impairment).

Change Intracortical Facilitation (ICF) From BaselineBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on intracortical facilitation (ICF) from baseline.

Change of Quality of Life From Baseline: EQ-5D-5L ScaleBaseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Change of quality of life from baseline evaluated with the EQ-5D-5L scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The scale ranges from 5 (no impairment) to 25 (severe impairment).

Trial Locations

Locations (1)

AO Spedali Civili

🇮🇹

Brescia, BS, Italy

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