Clinical trial NCT01569958: Transcranial Direct Current Stimulation as a Novel Therapeutic Approach in Amyotrophic Lateral Sclerosis
Official title: Transcranial Direct Current Stimulation as a Novel Therapeutic Approach in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Università degli Studi 'G. d'Annunzio' Chieti e Pescara
Sponsor class: OTHER
Collaborators: name: Catholic University, Italy
name: Federico II University
name: Ministero della Salute, Italy
First posted: 2012-04-03
Enrollment: 54
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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Decline of ALSFRS-R (ALS functional rating scale-revised) from baseline to 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Decline of muscle strength from baseline to 12 months
timeFrame: 12 months
measure: Change of upper motor neuron signs from baseline to 12 months
timeFrame: 12 months
measure: Decline of forced vital capacity (percent of predicted normal) from baseline to 12 months
timeFrame: 12 months
measure: Change of quality of life from baseline to 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Chieti
country: Italy
facility: Centro Regionale Malattie Neuromuscolari, Ospedale Clinicizzato "SS. Annunziata"
city: Napoli
country: Italy
facility: Azienda Policlinico Università Federico II
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli
Study officials:
affiliation: Università "G. d'Annunzio" di Chieti e Pescara, Dipartimento Neuroscienze ed Imaging, and ASL n. 2 Lanciano-Vasto-Chieti
name: Alessandra Lugaresi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: