Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis (tDCS_MND_2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04293484
Recruitment Status : Recruiting
First Posted : March 3, 2020
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Barbara Borroni, 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.


Condition or disease Intervention/treatment Phase
Motor Neuron Disease, Familial Amyotrophic Lateral Sclerosis With Dementia Device: Anodal bilateral motor cortex and cathodal spinal tDCS Device: Sham bilateral motor cortex and sham spinal tDCS Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : January 31, 2021


Arm Intervention/treatment
Experimental: Real tDCS - Real tDCS
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
10 sessions of anodal bilateral motor cortex and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)

Sham Comparator: Sham tDCS - Real tDCS
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
10 sessions of anodal bilateral motor cortex and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)

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




Primary Outcome Measures :
  1. Change in Muscle Strength From Baseline [ Time Frame: Baseline - 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 :
  1. Change in Short-interval Intracortical Inhibition (SICI) From Baseline [ Time Frame: Baseline - 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

  2. Change in the ALSFRS-R Score From Baseline [ Time Frame: Baseline - 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).

  3. Change of Quality of Life From Baseline: ALSAQ-40 Scale [ Time Frame: 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 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).


  4. Change of Quality of Life From Baseline: EQ-5D-5L Scale [ Time Frame: 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 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).

  5. Change of Quality of Life From Baseline: EQ-VAS Scale [ Time Frame: 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 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).

  6. Change in Caregiver Burden (CBI) [ Time Frame: 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).

  7. Change Intracortical Facilitation (ICF) From Baseline [ Time Frame: Baseline - 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04293484


Contacts
Layout table for location contacts
Contact: Barbara Borroni, MD 030 3995631 bborroni@inwind.it
Contact: Alberto Benussi, MD 030 3995631 benussialberto@gmail.com

Locations
Layout table for location information
Italy
AO Spedali Civili Recruiting
Brescia, BS, Italy, 25100
Contact: Barbara Borroni, MD    0039 030 3995631    bborroni@inwind.it   
Contact: Alberto Benussi, MD    0039 030 3995631    benussialberto@gmail.com   
Principal Investigator: Barbara Borroni, MD         
Sub-Investigator: Alberto Benussi, MD         
Sponsors and Collaborators
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Investigators
Layout table for investigator information
Principal Investigator: Barbara Borroni, MD Università degli Studi di Brescia
Principal Investigator: Alberto Benussi, MD Università degli Studi di Brescia
Publications:
Layout table for additonal information
Responsible Party: Barbara Borroni, Prof., Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
ClinicalTrials.gov Identifier: NCT04293484    
Other Study ID Numbers: NP2743 v2
First Posted: March 3, 2020    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia:
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Transcranial direct current stimulation
tDCS
Non-invasive brain stimulation
Transcranial magnetic stimulation
TMS
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases