Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Rehabilitative Trial With tDCS in Amyotrophic Lateral Sclerosis (tDCS_MND)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03293394
Recruitment Status : Completed
First Posted : September 26, 2017
Results First Posted : November 22, 2019
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Barbara Borroni, Azienda Ospedaliera Spedali Civili di Brescia

Tracking Information
First Submitted Date  ICMJE September 21, 2017
First Posted Date  ICMJE September 26, 2017
Results First Submitted Date  ICMJE November 4, 2019
Results First Posted Date  ICMJE November 22, 2019
Last Update Posted Date November 22, 2019
Actual Study Start Date  ICMJE October 2, 2017
Actual Primary Completion Date June 20, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
Change in Muscle Strength From Baseline [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2017)
Change in short-interval intracortical inhibition-facilitation (SICI-ICF) from baseline [ Time Frame: Baseline - 2 weeks ]
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on short-interval intracortical inhibition-facilitation (SICI-ICF) from baseline
Change History Complete list of historical versions of study NCT03293394 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
  • Change in Short-interval Intracortical Inhibition (SICI) From Baseline [ Time Frame: Baseline - 2 weeks - 2 months - 6 months ]
    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 [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
  • Change of Quality of Life From Baseline: ALSAQ-40 Scale [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
  • Change of Quality of Life From Baseline: EQ-5D-5L Scale [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
  • Change of Quality of Life From Baseline: EQ-VAS Scale [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
  • Change in Caregiver Burden (CBI) [ Time Frame: Baseline - 2 weeks - 2 months - 6 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).
  • Change Intracortical Facilitation (ICF) From Baseline [ Time Frame: Baseline - 2 weeks - 2 month - 6 months ]
    By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on intracortical facilitation (ICF) from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2017)
  • Change in short-interval intracortical inhibition-facilitation (SICI-ICF) from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on short-interval intracortical inhibition-facilitation (SICI-ICF) from baseline
  • Change in short-interval intracortical facilitation (SICF) from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on short-interval intracortical facilitation (SICF) from baseline
  • Change in long-interval intracortical inhibition (LICI) from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of tDCS on long-interval intracortical inhibition (LICI) from baseline
  • Decline in the ALSFRS-R score from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    Decline in the ALS Functional Rating Scale (ALSFRS-R) score from baseline
  • Decline of muscle strength from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    A megascore will be obtained by summing scores of single muscles manually evaluated according to the Medical Research Council (MRC) Scale
  • Change of quality of life from baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    Change of quality of life from baseline evaluated with the ALSAQ-40 scale
  • Change of blood neurofilaments [ Time Frame: Baseline - 2 weeks - 1 month - 3 month - 6 months ]
    Change of blood neurofilaments measures from baseline
  • Survival [ Time Frame: 12 months - 24 months ]
    Difference in survival between groups
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rehabilitative Trial With tDCS in Amyotrophic Lateral Sclerosis
Official Title  ICMJE Rehabilitative Trial With Transcranial Direct Current Stimulation (tDCS) in Amyotrophic Lateral Sclerosis
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, the investigators will evaluate whether a two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with amyotrophic lateral sclerosis and 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.

In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with amyotrophic lateral sclerosis and modulate intracortical connectivity, at short and long term.

Subjects will be randomized in two groups, one receiving a 10 day (5 days/week for 2 weeks) treatment with anodal bilateral motor cortex tDCS and cathodal spinal tDCS and the other receiving sham stimulation with identical parameters. After the intervention, patients will be reassessed with a clinical and neurophysiological evaluation at 2 weeks, 2 months and 6 months after treatment. Furthermore, blood neurofilaments will be measured at each time point.

Clinical evaluation will include the ALSFRS-R, ALSAQ-40, CBI, EQ-5D-5L, muscle strength evaluated with the MRC scale.

Neurophysiological evaluation will include measures of intracortical connectivity, evaluated with transcranial magnetic stimulation (TMS) as short interval intracortical inhibition (SICI-ICF), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • 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)
Study Arms  ICMJE
  • Experimental: Real tDCS
    10 days anodal bilateral motor cortex and cathodal spinal tDCS
    Intervention: Device: Anodal bilateral motor cortex and cathodal spinal tDCS
  • Placebo Comparator: Sham tDCS
    10 days sham bilateral motor cortex and sham spinal tDCS
    Intervention: Device: Sham bilateral motor cortex and sham spinal tDCS
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: September 25, 2017)
100
Actual Study Completion Date  ICMJE July 1, 2018
Actual Primary Completion Date June 20, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03293394
Other Study ID Numbers  ICMJE NP2743
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Barbara Borroni, Azienda Ospedaliera Spedali Civili di Brescia
Study Sponsor  ICMJE Azienda Ospedaliera Spedali Civili di Brescia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Barbara Borroni, MD Azienda Ospedaliera Spedali Civili, Brescia
PRS Account Azienda Ospedaliera Spedali Civili di Brescia
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP