Amyotrophic Lateral Sclerosis (ALS)
Conditions
Brief summary
Most ALS care is centered on patient support and symptom management, making rehabilitation an integral aspect for slowing disease progression, prolonging life span, and increasing quality of life. Brain stimulation has been increasingly explored as a promising neuromodulatory tool to prime motor function in several neurological disorders. We propose a novel mechanism using remotely supervised brain stimulation to preserve motor function in individuals with ALS. This project will also aim to explore the effectiveness of brain stimulation on upper and lower motor neuron mechanisms in individuals with ALS.
Interventions
OTHERTranscranial Direct Current Stimulation (tDCS)
Noninvasive brain stimulation
OTHERSham tDCS + anodal tDCS
Fake noninvasive brain stimulation or anodal noninvasive brain stimulation
Sponsors
University of Chicago
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of possible, probable, or definite amyotrophic lateral sclerosis according to El Escorial revised criteria * Spinal onset ALS with initial weakness in the upper or lower extremity. * Diagnosed with ALS within the past 5 years * 1-2 point change in pre-slope of the ALSFRS-R at time of enrollment (ratio of drop in score from 48 to the duration in months from onset of weakness) * Score ≥ 2 for swallowing of the ALSFRS-R * Score ≥ 2 for walking of the ALSFRS-R * Able to provide informed consent * Stable dose of riluzole, edaravone, AMX0035 (Relyvrio) or no medications * Availability of a caregiver for remote administration of tDCS
Exclusion criteria
* Subject has bulbar onset ALS * Any neurological diagnosis other than ALS * Psychiatric disorders * Any other concomitant disease that affects prognosis of ALS inclusive of systemic disease, cardiovascular disease, hepatic or renal disorder * Tracheostomal or noninvasive ventilation for more than 12 hours per day * Enrollment in an on-going ALS pharmaceutical trial * Subject plans on moving within 6 months. TMS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Revised ALS Functioning Rating Scale (ALSFRS-R) | Change from baseline to immediately after training and baseline to 3 months follow up. | This questionnaire evaluates function over time and disease progression in ALS patients with questions related to daily activities such as speech, swallowing, walking, etc. Scores range between 0-48 with higher scores corresponding to more function being retained. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Motor Control | Change from baseline to immediately after training and baseline to 3 months follow up. | The participant will track a computer-generated sinusoidal target with ankle dorsiflexion and plantarflexion in a custom-built ankle-tracking device. Accuracy of tracking the target with ankle motion will be calculated. |
| Quality of Life With EuroQol-5D (EQ-5D) | Change from baseline to immediately after training and baseline to 3 months follow up. | Quality of life will be measured with the EuroQol-5D (EQ-5D), a questionnaire with questions designed to assess aspects of quality of life. |
| EuroQual-Visual Analog Scale (EQ-VAS) | Change from baseline to immediately after training | Quality of life will be measured using a visual analog scale with endpoints labeled, 'The best health you can imagine' and 'the worst health you can imagine' in response to questions related to aspects of quality of life. Scores range from 0 to 100, with higher values indicating better self-rated health status. |
| Gait Speed | Change from baseline to immediately after training | Self-selected will be measured as the average walking speed from 2 trials of the 10-m walk test (10MWT). |
| Upper and Lower Motor Neuron Mechanisms Using Transcranial Magnetic Stimulation (TMS) | Change from baseline to immediately after training and baseline to 3 months follow up. | Upper and lower motor neuron mechanisms of the tibialis anterior will be measured using single pulse transcranial magnetic stimulation (TMS). Measures may include motor evoked potential (MEP) amplitude, latency, and/or cortical silent period. |
| Upper and Lower Motor Neuron Mechanisms Using Peripheral Nerve Stimulation (PNS) | Change from baseline to immediately after training and baseline to 3 months follow up. | Upper and lower motor neuron mechanisms in ALS will also be assessed using peripheral nerve stimulation at either the knee or the elbow. |
| Fatigue Severity Scale | Change from baseline to immediately after training. | 9-item scale measuring severity of fatigue and its effect on participant's daily activities and lifestyle with higher scores representing more fatigue and fatigue playing a larger role in daily activities. Minimum score = 0 and maximum score = 63. |
Countries
United States
Participant flow
Pre-assignment details
A total of 70 individuals were assessed for eligibility. Of these, 56 were excluded prior to randomization: 48 did not meet eligibility criteria and 8 declined to participate or were unable to commit due to logistical reasons. Fourteen participants were randomized (7 to the intervention group and 7 to the delayed-start group). All eligibility assessments and consent were conducted remotely or in person before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Direct Current Stimulation (tDCS) Facilitatory transcranial direct current stimulation (tDCS) | 7 |
| Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group Sham tDCS followed by a switch to anodal tDCS. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Transcranial Direct Current Stimulation (tDCS) | Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group | Total |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 9 | 55 years STANDARD_DEVIATION 10 | 54 years STANDARD_DEVIATION 9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 6 / 7 | 5 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Change in Revised ALS Functioning Rating Scale (ALSFRS-R)
This questionnaire evaluates function over time and disease progression in ALS patients with questions related to daily activities such as speech, swallowing, walking, etc. Scores range between 0-48 with higher scores corresponding to more function being retained.
Time frame: Change from baseline to immediately after training and baseline to 3 months follow up.
Population: Analyses were conducted on an intent-to-treat basis, including all randomized participants who received at least one session. Missing data were handled using the last observation carried forward (LOCF) approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Direct Current Stimulation (tDCS) | Change in Revised ALS Functioning Rating Scale (ALSFRS-R) | Pre to Post | -1 Change score on ALSFRS-R | Standard Error 1.06 |
| Transcranial Direct Current Stimulation (tDCS) | Change in Revised ALS Functioning Rating Scale (ALSFRS-R) | Pre to 3 month follow up | -3.2 Change score on ALSFRS-R | Standard Error 2 |
| Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group | Change in Revised ALS Functioning Rating Scale (ALSFRS-R) | Pre to Post | -7.1 Change score on ALSFRS-R | Standard Error 1.56 |
| Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group | Change in Revised ALS Functioning Rating Scale (ALSFRS-R) | Pre to 3 month follow up | -7.1 Change score on ALSFRS-R | Standard Error 1.56 |
Secondary
Ankle Motor Control
The participant will track a computer-generated sinusoidal target with ankle dorsiflexion and plantarflexion in a custom-built ankle-tracking device. Accuracy of tracking the target with ankle motion will be calculated.
Time frame: Change from baseline to immediately after training and baseline to 3 months follow up.
Secondary
EuroQual-Visual Analog Scale (EQ-VAS)
Quality of life will be measured using a visual analog scale with endpoints labeled, 'The best health you can imagine' and 'the worst health you can imagine' in response to questions related to aspects of quality of life. Scores range from 0 to 100, with higher values indicating better self-rated health status.
Time frame: Change from baseline to immediately after training
Secondary
Fatigue Severity Scale
9-item scale measuring severity of fatigue and its effect on participant's daily activities and lifestyle with higher scores representing more fatigue and fatigue playing a larger role in daily activities. Minimum score = 0 and maximum score = 63.
Time frame: Change from baseline to immediately after training.
Secondary
Gait Speed
Self-selected will be measured as the average walking speed from 2 trials of the 10-m walk test (10MWT).
Time frame: Change from baseline to immediately after training
Population: Gait speed data were collected for participants who were able to complete the 10MWT. Participants (n=6) who were non-ambulatory and could not perform the test at baseline or follow-up, and were therefore excluded from this analysis. Participants who withdrew from the study or did not complete the intervention are also not included in the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Direct Current Stimulation (tDCS) | Gait Speed | -0.11 m/s | Standard Error 0.1 |
| Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group | Gait Speed | -0.30 m/s | Standard Error 0.08 |
Secondary
Quality of Life With EuroQol-5D (EQ-5D)
Quality of life will be measured with the EuroQol-5D (EQ-5D), a questionnaire with questions designed to assess aspects of quality of life.
Time frame: Change from baseline to immediately after training and baseline to 3 months follow up.
Secondary
Upper and Lower Motor Neuron Mechanisms Using Peripheral Nerve Stimulation (PNS)
Upper and lower motor neuron mechanisms in ALS will also be assessed using peripheral nerve stimulation at either the knee or the elbow.
Time frame: Change from baseline to immediately after training and baseline to 3 months follow up.
Secondary
Upper and Lower Motor Neuron Mechanisms Using Transcranial Magnetic Stimulation (TMS)
Upper and lower motor neuron mechanisms of the tibialis anterior will be measured using single pulse transcranial magnetic stimulation (TMS). Measures may include motor evoked potential (MEP) amplitude, latency, and/or cortical silent period.
Time frame: Change from baseline to immediately after training and baseline to 3 months follow up.