Remotely Supervised tDCS for Slowing ALS Disease Progression

Study Overview
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Brief Summary
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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.

Official Title
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Remotely Supervised Transcranial Direct Current Stimulation for Slowing Disease Progression in Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Other: Transcranial Direct Current Stimulation (tDCS)
* Other: Sham tDCS + anodal tDCS


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Implanted cardiac pacemaker Metal implants in the head or face Unexplained, recurring headaches History of seizures or epilepsy Currently under medication that could increase motor excitability and lower seizure threshold Skull abnormalities or fractures Concussion within the last 6 months Currently pregnant tDCS Exclusion Criteria: Skin hypersensitivity History of contact dermatitis History of allodynia and/or hyperalgesia Any other skin or scalp condition that could be aggravated by tDCS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Direct Current Stimulation (tDCS)<br>Facilitatory transcranial direct current stimulation (tDCS) | Other: Transcranial Direct Current Stimulation (tDCS)<br>* Noninvasive brain stimulation<br>* Other names: Soterix Medical 1X1 tDCS mini-CT Stimulator;|
| Sham Comparator: Delayed-Start Transcranial Direct Current Stimulation (tDCS) Control Group<br>Sham tDCS followed by a switch to anodal tDCS. | Other: Sham tDCS + anodal tDCS<br>* Fake noninvasive brain stimulation or anodal noninvasive brain stimulation<br>* Other names: Soterix Medical 1X1 tDCS mini-CT Stimulator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 0-40 with higher scores corresponding to more function being retained. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| Muscle Strength Testing | Maximum strength of bilateral ankle dorsiflexors and knee extensors will be tested using a hand-held dynamometer and using the Medical Research Council (MRC) Scale for muscle strength. | Change from baseline to immediately after training and baseline to 3 months follow up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gait speed | Self-selected and fast walking will be measured as the average walking speed from 2 trials of the 10-m walk test (10MWT). | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 10-meter walk | The 10-meter walk test (10MWT) is a performance measure used to assess walking speed in meters per second over a short distance. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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. | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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). | Change from baseline to immediately after training and baseline to 3 months follow up. | 
| 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. | Change from baseline to immediately after training and baseline to 3 months follow up. |