Transcranial Direct Current Stimulation as a Novel Therapeutic Approach in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscular atrophy due to the degeneration and loss of motor neurons, the nerve cells that, in the central nervous system (motor cortex, brainstem and spinal chord), control voluntary movement. Riluzole, the only drug approved for ALS treatment, modestly slow disease progression.

Transcranial direct current stimulation (tDCS) is a noninvasive technique of neuromodulation that is currently studied as a possible therapeutic tool for several neurological and psychiatric diseases and has been found safe and well tolerated. Based on experimental evidence in animals and human subjects, tDCS is expected to reduce motor cortex excitability and excitotoxicity, that is neuronal injury induced by excessive glutamatergic stimulation, one of postulated pathophysiological mechanisms in ALS.

This study will investigate if transcranial direct current stimulation of motor cortex is useful in delaying disease progression and is well tolerated in ALS patients.

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: transcranial direct current stimulation; Other: Sham stimulation

Detailed Description

This is a double blind, randomized, placebo-controlled clinical trial.

Cathodic tDCS (1 mA for 20 minutes) will be sequentially applied over the motor cortex of both sides, for five consecutive days every month for twelve months. The control group will receive a sham stimulation that reproduce tactile sensation of real stimulation but has no effects on central nervous system. For stimulation, researchers will employ a CE-certified medical device acting as a micro-processor-controlled constant current source. All patients will take riluzole during the entire period of the study.

Fifty-four participants will be recruited from three Italian Centers and randomized to one of two arms of the study.

Disease progression and quality of life will be evaluated at baseline and every three months during the study.

At each visit adverse events will be reported and tolerability will be assessed through a specific questionnaire.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Chieti, Italy, 66013
    • Recruiting
    • Centro Regionale Malattie Neuromuscolari, Ospedale Clinicizzato "SS. Annunziata"
    • Contact: Margherita Capasso, MD, PhD; Phone Number: 00390871358585; Email: neurolab@unich.it
    • Principal Investigator: Alessandra Lugaresi, MD, PhD
    • Sub-Investigator: Margherita Capasso, MD,PhD
  • Napoli, Italy, 80131
    • Not yet recruiting
    • Azienda Policlinico Università Federico II
    • Principal Investigator: Lucio Santoro, MD
  • Rome, Italy, 00168
    • Not yet recruiting
    • Policlinico Universitario Agostino Gemelli
    • Principal Investigator: Vincenzo Di Lazzaro, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of probable, laboratory-supported probable, or definite amyotrophic lateral sclerosis according to the El Escorial revised criteria
• spinal onset
• aged 18 to 85 years inclusive
• disease duration ≤ 24 months
• disease progression in the past 3 months
• FVC ≥ 70% of predicted
• 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
• in 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:

• bulbar onset
• previous poliomyelitis
• motor neuron diseases other than ALS
• clinical involvement of other neurological systems
• pregnancy, lactation,or unwillingness to contraception if required
• possible contraindications to tDCS: metals in the head (excluding the mouth); electromedical devices; seizures; drugs or neurological conditions lowering seizure threshold; alcoholism; severe heart diseases
• any severe disease other than ALS
• experimental drugs within 1 month prior to enrollment
• drugs potentially modifying the response to tDCS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: tDCS	Other: transcranial direct current stimulation; transcranial direct current stimulation applied to the motor cortex of both sides (1 mA, 20 minutes) for five consecutive days every month for 12 months
SHAM_COMPARATOR: sham	Other: Sham stimulation; 1 mA stimulation for 30 seconds every 900 seconds per session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decline of ALSFRS-R (ALS functional rating scale-revised) from baseline to 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decline of muscle strength from baseline to 12 months	A megascore will be obtained by summing scores of single muscles manually tested according to the Medical Research Council Scale	12 months
Change of upper motor neuron signs from baseline to 12 months	A score will be obtained based on presence/absence of listed upper motor neuron signs and grade of spasticity	12 months
Decline of forced vital capacity (percent of predicted normal) from baseline to 12 months		12 months
Change of quality of life from baseline to 12 months	The ALSAQ-40 questionnaire will be employed	12 months

Collaborators and Investigators

• Sponsor: Università degli Studi 'G. d'Annunzio' Chieti e Pescara
• Collaborators: Federico II University; Catholic University, Italy; Ministero della Salute, Italy
• Investigators: Principal Investigator: Alessandra Lugaresi, MD, PhD, Università "G. d'Annunzio" di Chieti e Pescara, Dipartimento Neuroscienze ed Imaging, and ASL n. 2 Lanciano-Vasto-Chieti

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ANTICIPATED): April 1, 2016
• Study Completion (ANTICIPATED): April 1, 2016

Study Registration Dates

• First Submitted: March 9, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (ESTIMATE): April 3, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 10, 2012
• Last Update Submitted That Met QC Criteria: October 8, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: TDCS2011-01; RF-ABR-2007-631680 (OTHER_GRANT: Italian Ministry of Health/RF-ABR-2007-631680)