Cervical Electrical Stimulation for ALS

NCT ID: NCT03411863

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-04
• Study Completion Date: 2021-06-01

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Participants without neurological disease

Participants without neurological disease. All subjects undergo the same full protocol.

Group Type: ACTIVE_COMPARATOR

CES at rest

Intervention Type: DEVICE

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 plus active hand or wrist movements

Intervention Type: DEVICE

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.

Participants with ALS

Participants with ALS. All subjects undergo the same full protocol.

Group Type: EXPERIMENTAL

CES at rest

Intervention Type: DEVICE

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 plus active hand or wrist movements

Intervention Type: DEVICE

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.

Interventions

CES at rest

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.

Intervention Type: DEVICE

CES plus active hand or wrist movements

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age between 21 and 75 years
• Diagnosis of probable or definite ALS (or non-disabled volunteer)
• Incomplete weakness of left or right wrist or hand muscles:

• score of 2, 3, or 4 (out of 5) on manual muscle testing of:
• wrist flexion
• finger extension
• finger flexion
• or finger abduction
• Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation and/or adductor digiti minimi (ADM) to ulnar nerve stimulation
• US Veteran or non-Veteran

• Age between 21 and 75 years
• No history of significant neurological disease
• Detectable F-wave responses of the left or right APB to median nerve stimulation and/or ADM to ulnar nerve stimulation
• US Veteran or non-Veteran

Exclusion Criteria

• History of other serious injury or disease of central or peripheral nervous system
• History of seizures
• Ventilator dependence or patent tracheostomy site
• Use of medications that significantly lower seizure threshold
• History of head trauma with evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging
• History of implanted:

• brain/spine/nerve stimulators
• aneurysm clips
• ferromagnetic metallic implants
• or cardiac pacemaker/defibrillator
• Significant coronary artery or cardiac conduction disease
• History of bipolar disorder or suicide attempt or active psychosis
• Heavy alcohol consumption (> equivalent of 5 oz of liquor) within previous 48 hours
• Open skin lesions over the face, neck, shoulders, or arms
• Pregnancy
• Unsuitable for study participation as determined by study physician

• History of other serious injury or disease of central or peripheral nervous system
• History of seizures
• Ventilator dependence or patent tracheostomy site
• Use of medications that significantly lower seizure threshold
• History of head trauma with evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging
• History of implanted:

• brain/spine/nerve stimulators
• aneurysm clips
• ferromagnetic metallic implants
• or cardiac pacemaker/defibrillator
• Significant coronary artery or cardiac conduction disease
• History of bipolar disorder or suicide attempt or active psychosis
• Heavy alcohol consumption (> equivalent of 5 oz of liquor) within previous 48 hours
• Open skin lesions over the face, neck, shoulders, or arms
• Pregnancy
• Unsuitable for study participation as determined by study physician

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noam Y. Harel, MD PhD

Role: PRINCIPAL_INVESTIGATOR

James J. Peters Veterans Affairs Medical Center

Locations

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

B2527-P

Identifier Type: -

Identifier Source: org_study_id