Back to resultsCortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis (tDCS_MND_2)
Primary Purpose
Motor Neuron Disease, Familial, Amyotrophic Lateral Sclerosis With Dementia
Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Anodal bilateral motor cortex and cathodal spinal tDCS
Sham bilateral motor cortex and sham spinal tDCS
Sponsored by
About this trial
This is an interventional treatment trial for Motor Neuron Disease, Familial focused on measuring Motor Neuron Disease, Amyotrophic Lateral Sclerosis, Transcranial direct current stimulation, tDCS, Non-invasive brain stimulation, Transcranial magnetic stimulation, TMS
Eligibility 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
Sites / Locations
- AO Spedali Civili
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Real tDCS - Real tDCS
Sham tDCS - Real tDCS
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Change in Short-interval Intracortical Inhibition (SICI) From Baseline
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 Baseline
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 of Quality of Life From Baseline: ALSAQ-40 Scale
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-5D-5L Scale
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).
Change of Quality of Life From Baseline: EQ-VAS Scale
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 Caregiver Burden (CBI)
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 Intracortical Facilitation (ICF) From Baseline
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on intracortical facilitation (ICF) from baseline.
Full Information
NCT ID
NCT04293484
First Posted
March 1, 2020
Last Updated
October 20, 2022
Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
1. Study Identification
Unique Protocol Identification Number
NCT04293484
Brief Title
Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis
Acronym
tDCS_MND_2
Official Title
Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
March 12, 2018 (Actual)
Primary Completion Date
July 31, 2022 (Actual)
Study Completion Date
July 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Real tDCS - Real tDCS
Arm Type
Experimental
Arm Description
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)
Arm Title
Sham tDCS - Real tDCS
Arm Type
Sham Comparator
Arm Description
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)
Intervention Type
Device
Intervention Name(s)
Anodal bilateral motor cortex and cathodal spinal tDCS
Intervention Description
10 sessions of anodal bilateral motor cortex and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)
Intervention Type
Device
Intervention Name(s)
Sham bilateral motor cortex and sham spinal tDCS
Intervention Description
10 sessions of sham bilateral motor cortex and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks)
Primary Outcome Measure Information:
Title
Change in Muscle Strength From Baseline
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Secondary Outcome Measure Information:
Title
Change in Short-interval Intracortical Inhibition (SICI) From Baseline
Description
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on 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
Title
Change in the ALSFRS-R Score From Baseline
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Title
Change of Quality of Life From Baseline: ALSAQ-40 Scale
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Title
Change of Quality of Life From Baseline: EQ-5D-5L Scale
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Title
Change of Quality of Life From Baseline: EQ-VAS Scale
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Title
Change in Caregiver Burden (CBI)
Description
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).
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
Title
Change Intracortical Facilitation (ICF) From Baseline
Description
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on intracortical facilitation (ICF) from baseline.
Time Frame
Baseline - 2 weeks - 2 month - 6 months - 6 months and 2 weeks - 8 months - 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Borroni, MD
Organizational Affiliation
Università degli Studi di Brescia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alberto Benussi, MD
Organizational Affiliation
Università degli Studi di Brescia
Official's Role
Principal Investigator
Facility Information:
Facility Name
AO Spedali Civili
City
Brescia
State/Province
BS
ZIP/Postal Code
25100
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31204206
Citation
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.
Results Reference
background
PubMed Identifier
27866120
Citation
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.
Results Reference
background
PubMed Identifier
25843898
Citation
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. Erratum In: Lancet Neurol. 2015 Jun;14(6):566.
Results Reference
background
PubMed Identifier
21840887
Citation
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.
Results Reference
background
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Cortico-Spinal tDCS as Rehabilitative Intervention in Amyotrophic Lateral Sclerosis
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