Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis

NCT04293484 | Completed

• 1 other identifier: NP2743 v2
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Change in Muscle Strength From Baseline

  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).

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Secondary Outcomes (7)

• Change in Short-interval Intracortical Inhibition (SICI) From Baseline

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

• Change in the ALSFRS-R Score From Baseline

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

• Change of Quality of Life From Baseline: ALSAQ-40 Scale

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

• Change of Quality of Life From Baseline: EQ-5D-5L Scale

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

• Change of Quality of Life From Baseline: EQ-VAS Scale

  Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months

Study Arms (2)

Real tDCS - Real tDCS

EXPERIMENTAL

10 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)

Device: Anodal bilateral motor cortex and cathodal spinal tDCS

Sham tDCS - Real tDCS

SHAM COMPARATOR

10 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)

Device: Anodal bilateral motor cortex and cathodal spinal tDCS; Device: Sham bilateral motor cortex and sham spinal tDCS

Interventions

Anodal bilateral motor cortex and cathodal spinal tDCS DEVICE

10 sessions of anodal bilateral motor cortex and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)

Real tDCS - Real tDCS; Sham tDCS - Real tDCS

Sham bilateral motor cortex and sham spinal tDCS DEVICE

10 sessions of sham bilateral motor cortex and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks)

Sham tDCS - Real tDCS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

AO Spedali Civili

Brescia, BS, 25100, Italy

Location

Related Publications (5)

• 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.

  PMID: 31204206 BACKGROUND

• 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.

  PMID: 27866120 BACKGROUND

• 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.

  PMID: 25843898 BACKGROUND

• 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.

  PMID: 21840887 BACKGROUND

• Benussi A, Cantoni V, Grassi M, Libri I, Cotelli MS, Tarantino B, Datta A, Thomas C, Huber N, Karkkainen S, Herukka SK, Haapasalo A, Filosto M, Padovani A, Borroni B. 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.

  PMID: 37977335 DERIVED

MeSH Terms

Conditions

Motor Neuron Disease; Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Barbara Borroni, MD

  Università degli Studi di Brescia

  PRINCIPAL INVESTIGATOR

• Alberto Benussi, MD

  Università degli Studi di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: March 1, 2020
• First Posted: March 3, 2020
• Study Start: March 12, 2018
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: October 21, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)