Trial Outcomes & Findings for Rehabilitative Trial With tDCS in Amyotrophic Lateral Sclerosis (NCT NCT03293394)

NCT ID: NCT03293394

Last Updated: 2020-03-03

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 30 participants
• Primary outcome timeframe: Baseline - 2 weeks - 2 months - 6 months
• Results posted on: 2020-03-03

Participant Flow

Participant milestones

Measure	Real tDCS 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS 10 days sham bilateral motor cortex and sham spinal tDCS 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)
First Intervention (2 Weeks) STARTED	20	10
First Intervention (2 Weeks) COMPLETED	20	10
First Intervention (2 Weeks) NOT COMPLETED	0	0
Follow-up (6 Months) STARTED	20	10
Follow-up (6 Months) COMPLETED	16	8
Follow-up (6 Months) NOT COMPLETED	4	2

Reasons for withdrawal

Measure	Real tDCS 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Follow-up (6 Months) Adverse Event	4	2

Baseline Characteristics

Rehabilitative Trial With tDCS in Amyotrophic Lateral Sclerosis

Baseline characteristics by cohort

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)	Total n=30 Participants Total of all reporting groups
Age, Continuous	60.5 years STANDARD_DEVIATION 10.9 • n=5 Participants	63.9 years STANDARD_DEVIATION 11.3 • n=7 Participants	61.7 years STANDARD_DEVIATION 2.0 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Italy	20 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants
Disease Duration	2.1 years STANDARD_DEVIATION 1.4 • n=5 Participants	1.8 years STANDARD_DEVIATION 1.0 • n=7 Participants	2.0 years STANDARD_DEVIATION 0.2 • n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change in Muscle Strength From Baseline 2 Months	76.4 units on a scale Standard Deviation 0.4	72.9 units on a scale Standard Deviation 0.6
Change in Muscle Strength From Baseline Baseline	74.7 units on a scale Standard Deviation 0.0	74.7 units on a scale Standard Deviation 0.0
Change in Muscle Strength From Baseline 2 Weeks	76.4 units on a scale Standard Deviation 0.2	74.5 units on a scale Standard Deviation 0.3
Change in Muscle Strength From Baseline 6 Months	75.9 units on a scale Standard Deviation 0.6	72.0 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change in Short-interval Intracortical Inhibition (SICI) From Baseline Baseline	1.0 millivolts Standard Deviation 0.1	1.0 millivolts Standard Deviation 0.1
Change in Short-interval Intracortical Inhibition (SICI) From Baseline 2 weeks	0.4 millivolts Standard Deviation 0.1	1.0 millivolts Standard Deviation 0.1
Change in Short-interval Intracortical Inhibition (SICI) From Baseline 2 Months	0.5 millivolts Standard Deviation 0.1	0.9 millivolts Standard Deviation 0.1
Change in Short-interval Intracortical Inhibition (SICI) From Baseline 6 Months	0.6 millivolts Standard Deviation 0.1	1.0 millivolts Standard Deviation 0.1

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change in the ALSFRS-R Score From Baseline Baselin	31.5 units on a scale Standard Deviation 0.0	31.5 units on a scale Standard Deviation 0.0
Change in the ALSFRS-R Score From Baseline 2 Weeks	32.5 units on a scale Standard Deviation 0.2	31.8 units on a scale Standard Deviation 0.3
Change in the ALSFRS-R Score From Baseline 2 Months	32.0 units on a scale Standard Deviation 0.4	30.4 units on a scale Standard Deviation 0.5
Change in the ALSFRS-R Score From Baseline 6 Months	30.4 units on a scale Standard Deviation 0.5	29.7 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change of Quality of Life From Baseline: ALSAQ-40 Scale Baseline	45.0 units on a scale Standard Deviation 0.0	45.0 units on a scale Standard Deviation 0.0
Change of Quality of Life From Baseline: ALSAQ-40 Scale 2 Weeks	40.1 units on a scale Standard Deviation 2.0	38.3 units on a scale Standard Deviation 2.8
Change of Quality of Life From Baseline: ALSAQ-40 Scale 2 Months	38.8 units on a scale Standard Deviation 1.8	41.0 units on a scale Standard Deviation 2.5
Change of Quality of Life From Baseline: ALSAQ-40 Scale 6 Months	41.9 units on a scale Standard Deviation 2.2	42.4 units on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change of Quality of Life From Baseline: EQ-5D-5L Scale Baseline	13.0 units on a scale Standard Deviation 0.0	13.0 units on a scale Standard Deviation 0.0
Change of Quality of Life From Baseline: EQ-5D-5L Scale 2 Weeks	12.2 units on a scale Standard Deviation 0.5	13.6 units on a scale Standard Deviation 0.8
Change of Quality of Life From Baseline: EQ-5D-5L Scale 2 Months	12.6 units on a scale Standard Deviation 0.5	14.2 units on a scale Standard Deviation 0.7
Change of Quality of Life From Baseline: EQ-5D-5L Scale 6 Months	13.3 units on a scale Standard Deviation 0.6	14.3 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change of Quality of Life From Baseline: EQ-VAS Scale Baseline	51.6 units on a scale Standard Deviation 0.0	51.6 units on a scale Standard Deviation 0.0
Change of Quality of Life From Baseline: EQ-VAS Scale 2 Weeks	56.3 units on a scale Standard Deviation 2.0	46.1 units on a scale Standard Deviation 2.8
Change of Quality of Life From Baseline: EQ-VAS Scale 2 Months	53.2 units on a scale Standard Deviation 2.2	42.7 units on a scale Standard Deviation 3.1
Change of Quality of Life From Baseline: EQ-VAS Scale 6 Months	54.7 units on a scale Standard Deviation 2.9	40.2 units on a scale Standard Deviation 4.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change in Caregiver Burden (CBI) Baseline	26.7 units on a scale Standard Deviation 0.0	26.7 units on a scale Standard Deviation 0.0
Change in Caregiver Burden (CBI) 2 Weeks	21.6 units on a scale Standard Deviation 1.1	30.0 units on a scale Standard Deviation 1.5
Change in Caregiver Burden (CBI) 2 Months	24.0 units on a scale Standard Deviation 1.4	30.4 units on a scale Standard Deviation 1.9
Change in Caregiver Burden (CBI) 6 Months	24.8 units on a scale Standard Deviation 1.3	30.7 units on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Real tDCS n=20 Participants 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 Participants 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Change Intracortical Facilitation (ICF) From Baseline Baselin	1.8 millivolts Standard Deviation 0.1	1.7 millivolts Standard Deviation 0.1
Change Intracortical Facilitation (ICF) From Baseline 2 Weeks	1.3 millivolts Standard Deviation 0.0	1.7 millivolts Standard Deviation 0.1
Change Intracortical Facilitation (ICF) From Baseline 2 Months	1.4 millivolts Standard Deviation 0.1	1.7 millivolts Standard Deviation 0.1
Change Intracortical Facilitation (ICF) From Baseline 6 Months	1.6 millivolts Standard Deviation 0.0	1.6 millivolts Standard Deviation 0.1

Adverse Events

Real tDCS

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham tDCS

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Real tDCS n=20 participants at risk 10 days anodal bilateral motor cortex and cathodal spinal tDCS 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 tDCS n=10 participants at risk 10 days sham bilateral motor cortex and sham spinal tDCS 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)
Respiratory, thoracic and mediastinal disorders Pneumonia	5.0% 1/20 • Number of events 1 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	20.0% 2/10 • Number of events 2 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	10.0% 2/20 • Number of events 2 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/10 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Worsening of Global Clinical Conditions	5.0% 1/20 • Number of events 1 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/10 • 6 Months follow-up Adverse event has been defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

Other adverse events

Adverse event data not reported

Additional Information

Prof. Barbara Borroni

Spedali Civili di Brescia

Phone: +39 0303995631

Email: bborroni@inwind.it

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place