Paired Stimulation to Increase Cortical Transmission to Hand Muscles: Pilot Study

Study Purpose:

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Device

Study Status:

Active, currently recruiting

Phase:

Not Applicable

Study Chair(s)/Principal Investigator(s):

Noam Y. Harel, MD, PhD, James J. Peters VA Medical Center

Clinicaltrials.gov ID (11 digit #):

NCT02469675

Neals Affiliated?

No

Coordinating Center Contact Information

James J. Peters VA Medical Center
Noam Y Harel, MD, PhD; Angelica Romero, BS / .(JavaScript must be enabled to view this email address) / (718) 584-9000 ext 1742; (718) 584-9000 ext 3123
.(JavaScript must be enabled to view this email address) Bronx, New York 10468 United States

Full Study Summary:

Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits may be an important method to improve functional recovery.

In this study, the investigators aim to use non-invasive magnetic and electrical stimulation to strengthen motor circuits between the brain and hands. Magnetic stimulation will be used over the motor cortex (scalp). Two methods of electrical stimulation will be compared: stimulation of the median nerve at the wrist; or direct stimulation of the cervical spinal cord across the skin on the back of the neck. Several different combinations of magnetic and electrical stimulation will be compared to find the conditions that best strengthen nerve circuits between the brain and hands - "Fire Together, Wire Together".

PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS STUDY. If we see temporary changes in this study, then future studies would focus on how to prolong that effect.

Detailed Description:

Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits represents a critical method to improve functional recovery. Different forms of magnetic and electrical stimulation have been used to activate brain, spinal cord, nerve, or muscle tissue. Although in some cases, surgically implanted electrical stimulation has delivered tremendous benefit, a non-invasive approach to nerve stimulation is preferable.

In this proposed study, the investigators aim to use non-invasive magnetic and electrical stimulation to strengthen motor circuits between the brain and hands. Transcranial magnetic stimulation (TMS) will be combined with either electrical stimulation of the median nerve at the wrist; or electrical transcutaneous stimulation of the cervical spinal cord. Magnetic and electrical stimulation will be precisely timed so that the pulses arrive at the target spinal motor neurons at roughly the same time - this precise timing is responsible for the phenomenon of "spike timing-dependent plasticity".

Two groups of participants will be studied: individuals with chronic incomplete cervical SCI (n=12), and individuals with definite or probable ALS (n=6). Subjects will undergo one 20-minute session each of unpaired or paired magnetic and electrical stimulation (8 visits on different days). Functional and physiological testing will be conducted prior to each intervention, then at 0, 15, 30, and 90 minutes post each intervention. Key measures include grip strength dynamometry, timed performance on a hand dexterity test, amplitude of abductor pollicis brevis (APB) response to TMS, integrated amplitude of APB F-wave responses, and duration of the 'cortical silent period' after TMS stimulation during APB contraction.

PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS STUDY. If we see temporary changes in this study, then future studies would focus on how to prolong that effect.

Study Sponsor:

Bronx VA Medical Center

Participant Duration:

Estimated Enrollment:

18

Estimated Study Start Date:

05/31/2015

Estimated Study Completion Date:

07/31/2016

Posting Last Modified Date:

11/02/2016

Date Study Added to alsconsortium.org:

08/19/2015
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    21

    Maximum Age:

    65

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Inclusion Criteria:
    -Chronic (>12 months since injury) incomplete SCI between levels C5-C8 or diagnosis of definite or probable ALS;
    -Incomplete weakness of left or right hand muscles: score of 3 or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction;
    -Detectable F-wave responses of the left or right abductor pollicis brevis muscle to median nerve stimulation;
    -Detectable motor evoked potentials in left or right abductor pollicis brevis muscle to transcranial magnetic stimulation.

    Exclusion Criteria:
    -Multiple spinal cord lesions;
    -History of seizures;
    -Ventilator dependence or patent tracheostomy site;
    -Use of medications that significantly lower seizure threshold, such as tricyclic antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion;
    -History of stroke, brain tumor, brain abscess, or multiple sclerosis;
    -History of moderate to severe head trauma (loss of consciousness for greater than one hour or 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 autonomic dysreflexia;
    -History of bipolar disorder;
    -History of suicide attempt;
    -Active psychosis;
    -Heavy alcohol consumption (greater than 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.

  • Site Contact Information

    J. Peters VA Medical Center
    Noam Y Harel, MD, PhD; Angelica Romero, BS / .(JavaScript must be enabled to view this email address) / (718) 584-9000 ext 1742; (718) 584-9000 ext 3123
    Bronx, New York 10468
    United States