ClinicalTrials.gov
ClinicalTrials.gov Menu

Cervical Electrical Stimulation for ALS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03411863
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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.


Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Device: CES at rest Device: CES plus active hand or wrist movements Not Applicable

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 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Noninvasive Cervical Electrical Stimulation for ALS: Mechanistic and Safety Study
Actual Study Start Date : January 4, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : May 29, 2020


Arm Intervention/treatment
Experimental: All subjects
All subjects undergo same full protocol, including CES at rest and CES plus active hand or wrist movements.
Device: 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.


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.





Primary Outcome Measures :
  1. Electromyographic responses (rest) [ Time Frame: up to 1 day ]
    Response to electrical and magnetic stimulation, singly or in combination, will be measured via peak-to-peak amplitude (millivolts) in first dorsal interosseous and abductor pollicis brevis muscles of conditioned relative to non-conditioned stimuli.

  2. Electromyographic responses (active) [ Time Frame: up to 1 day ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age between 21 and 65 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 extension
    • wrist flexion
    • finger extension
    • finger flexion
    • or finger abduction
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03411863


Contacts
Contact: Jonah M Levine, BA (718) 584-9000 ext 3123 jonah.levine@va.gov
Contact: Noam Y Harel, MD PhD (718) 584-9000 ext 1742 Noam.Harel@va.gov

Locations
United States, New York
James J. Peters VA Medical Center, Bronx, NY Recruiting
Bronx, New York, United States, 10468
Contact: Jonah M Levine, BA    718-584-9000 ext 3123    jonah.levine@va.gov   
Contact: Noam Y Harel, MD PhD    (718) 584-9000 ext 1742    Noam.Harel@va.gov   
Principal Investigator: Noam Y. Harel, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Noam Y. Harel, MD PhD James J. Peters Veterans Affairs Medical Center

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03411863     History of Changes
Other Study ID Numbers: B2527-P
First Posted: January 26, 2018    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 CFR Part 1.466.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: At time of publication.
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.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
Transcutaneous Electric Nerve Stimulation
transcranial magnetic stimulation

Additional relevant MeSH terms:
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases