Cervical Electrical Stimulation for ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional

Summary: 
      Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral
      sclerosis (ALS). ALS causes degeneration of motor neurons in both the brain and the spinal
      cord. Evidence from studies in people with spinal cord injury suggests that activating spared
      nerve circuits with electromagnetic stimulation improves nerve transmission.

      With this goal, the investigators have developed a novel method of noninvasive cervical
      (neck) electrical stimulation (CES). In this study, the investigators will investigate CES
      for its potential to strengthen nerve circuits to the hands in ALS.

      To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested
      previously. This study will be performed in two stages: First, basic experiments will be
      performed to better understand how CES interacts with other types of electrical and magnetic
      stimulations over the brain and peripheral nerves. Second, experiments will be performed to
      determine the types of CES that can facilitate active arm and hand movements.

      These experiments will improve understanding of electrical stimulation in ALS, and may set
      the table for future treatments.

      Both United States Veterans and non-Veterans are eligible to participate in this study.
    

Detailed description: 
      Amyotrophic lateral sclerosis (ALS) reduces connections between the cortical motor neurons
      that initiate movement and the spinal motor neurons that direct muscles to execute movement.
      This situation shares many key features with incomplete spinal cord injury (SCI).
      Accumulating evidence in SCI suggests that externally activating spared nerve circuits with
      electromagnetic stimulation augments neural transmission.

      With this goal, the investigators developed a novel method of noninvasive cervical electrical
      stimulation (CES). CES activates multiple muscles on both upper limbs by triggering afferent
      sensory or efferent motor nerve roots depending on stimulus intensity. This study will
      investigate CES for its potential to strengthen residual circuits to the hands in ALS.

      To the investigators' knowledge, electrical spinal stimulation for ALS has never been tested
      or applied previously. Therefore, a pilot study is essential. This study will be performed in
      two stages:

        1. Map CES circuit and synaptic targets: The experiments share a common structure
           comprising conditioning and test stimuli delivered at a range of intensities, sites, and
           interstimulus intervals.

        2. Determine parameters for combining CES with volitional movement: volitional limb
           movements depend on the same corticospinal and motor neuron circuits as those activated
           by TMS and F-waves. Since preliminary data shows that subthreshold CES facilitates
           transcranial magnetic stimulation (TMS) responses, CES may also be able to facilitate
           volitional limb movements.

      Successful completion of these experiments will: mechanistically elucidate CES circuit
      interactions; investigate the potential for CES to enhance concurrent volitional muscle
      activation; and establish CES as safe and feasible in the ALS population. Given the limited
      treatment options for ALS, any amount of progress would represent a meaningful step forward.
      Moreover, results of this pilot study could lead to direct translation for lasting clinical
      benefit by combining repetitive subthreshold CES with repetitive task-oriented physical
      exercise training in subsequent studies. CES would be compatible with other interventions,
      including medications and cell-based treatments.
    

Intervention name(s): CES at rest; CES plus active hand or wrist movements
Intervention type(s): Device; Device
Intervention description(s): CES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex.
This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits.; CES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort.
This is an experiment designed to detect momentary changes in muscle function.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Transcutaneous Electric Nerve Stimulation; transcranial magnetic stimulation