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Cervical Electrical Stimulation for ALS

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

CES at rest

CES plus active hand or wrist movements

About this trial

This is an interventional basic science trial for Amyotrophic Lateral Sclerosis focused on measuring Transcutaneous Electric Nerve Stimulation, transcranial magnetic stimulation

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (ALS):

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

Inclusion Criteria (Participants without neurological disease):

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 (ALS):

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

Exclusion Criteria: (Participants without neurological disease)

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

Sites / Locations

James J. Peters VA Medical Center, Bronx, NY

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Participants without neurological disease

Participants with ALS

Arm Description

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

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

Outcomes

Primary Outcome Measures

Electromyographic (EMG) Responses (Rest)

These results are derived from peak-to-peak EMG amplitude in the abductor pollicis brevis (APB) muscle in response to transcranial magnetic stimulation (TMS). Values represent the ratio of peak-to-peak APB amplitude when TMS is paired with cervical electrical stimulation (CES) at the indicated timing (in milliseconds) normalized to the response to TMS alone (control).

Electromyographic Responses (Active)

Effect of CES on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.

Secondary Outcome Measures

Full Information

NCT ID

NCT03411863

First Posted

January 5, 2018

Last Updated

September 26, 2022

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT03411863

Brief Title

Cervical Electrical Stimulation for ALS

Official Title

Noninvasive Cervical Electrical Stimulation for ALS: Mechanistic and Safety Study

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

January 4, 2018 (Actual)

Primary Completion Date

June 1, 2021 (Actual)

Study Completion Date

June 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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: 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Transcutaneous Electric Nerve Stimulation, transcranial magnetic stimulation

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Participants without neurological disease

Arm Type

Active Comparator

Arm Description

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

Arm Title

Participants with ALS

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

CES at rest

Intervention Description

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

Intervention Name(s)

CES plus active hand or wrist movements

Intervention Description

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.

Primary Outcome Measure Information:

Title

Electromyographic (EMG) Responses (Rest)

Description

Time Frame

up to 1 day

Title

Electromyographic Responses (Active)

Description

Effect of CES on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.

Time Frame

up to 1 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (ALS): 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 Inclusion Criteria (Participants without neurological disease): 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 (ALS): 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 Exclusion Criteria: (Participants without neurological disease) 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Noam Y. Harel, MD PhD

Organizational Affiliation

James J. Peters Veterans Affairs Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

James J. Peters VA Medical Center, Bronx, NY

City

Bronx

State/Province

New York

ZIP/Postal Code

10468

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

A Limited Dataset (LDS), with individual electrophysiological and physiological outcome measures, will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 Code of Federal Regulations (CFR) Part 1.466.

IPD Sharing Time Frame

At time of publication.

IPD Sharing Access Criteria

A Limited Dataset (LDS) will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 CFR Part 1.466.

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Cervical Electrical Stimulation for ALS

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