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Brain and Nerve Stimulation for Hand Muscles in Spinal Cord Injury and 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02469675
Recruitment Status : Completed
First Posted : June 11, 2015
Last Update Posted : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Noam Y. Harel, MD, PhD, Bronx VA Medical Center

Tracking Information
First Submitted Date  ICMJE June 9, 2015
First Posted Date  ICMJE June 11, 2015
Last Update Posted Date October 1, 2018
Study Start Date  ICMJE June 2015
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2016)
  • Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
  • Hand dexterity [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
    Timed performance on a grooved pegboard task.
  • Safety and tolerability [ Time Frame: Assessed periodically during each session. ]
    Vital signs are monitored throughout procedure; symptoms and degree of pain/discomfort are checked frequently.
Original Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
  • Hand dexterity [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
    Timed performance on a grooved pegboard task.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2015)
  • Grip strength [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
    Strength will be quantified using hand-held wireless dynamometry.
  • Change in the duration of the 'cortical silent period' after TMS stimulation during APB contraction [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
  • F-wave responses of the APB muscle [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Grip strength [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
    Strength will be quantified using hand-held wireless dynamometry.
  • H-reflex responses of the flexor carpi radialis (FCR) muscle [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
  • Change in the duration of the 'cortical silent period' after TMS stimulation during APB contraction [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
  • F-wave responses of the APB muscle [ Time Frame: Assessed pre, then 0, 15, 30, and 90 minutes post-intervention. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brain and Nerve Stimulation for Hand Muscles in Spinal Cord Injury and ALS
Official Title  ICMJE Paired Stimulation to Increase Cortical Transmission to Hand Muscles: Pilot Study
Brief 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".

Three groups of participants will be studied: individuals with chronic incomplete cervical SCI (n=12), individuals with definite or probable ALS (n=6), and individuals without neurological injury or disease (n=12). Subjects with SCI or ALS will have one screening visit to confirm eligibility for the study. All subjects will then undergo one baseline testing session followed by 7 sessions of unpaired or paired magnetic and electrical stimulation. Functional and physiological testing will be conducted prior to each stimulation session, then at 0, 15, 30, and 90 minutes post each session. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Spinal Cord Injury (SCI)
  • Amyotrophic Lateral Sclerosis (ALS)
Intervention  ICMJE
  • Device: Transcranial magnetic stimulation
    One TMS pulse every 10 seconds for 20 minutes
    Other Name: MagPro R30
  • Device: Median nerve stimulation
    One median nerve pulse every 10 seconds for 20 minutes
    Other Name: Digitimer DS7A
  • Device: Cervical transcutaneous stimulation
    One cervical pulse every 10 seconds for 20 minutes
    Other Name: Digitimer DS7A
Study Arms  ICMJE Experimental: All subjects

All subjects undergo same full protocol, including different combinations of stimulation on different days:

Transcranial Magnetic Stimulation Cervical Transcutaneous Stimulation Median Nerve Stimulation

Interventions:
  • Device: Transcranial magnetic stimulation
  • Device: Median nerve stimulation
  • Device: Cervical transcutaneous stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 28, 2018)
39
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2015)
18
Actual Study Completion Date  ICMJE July 31, 2018
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or females age 21-65 years;
  • No history of serious neurological injury or disease; OR
  • Chronic (>12 months since injury) incomplete SCI between levels C2-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;
  • Recurrent history over the last 6 months 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02469675
Other Study ID Numbers  ICMJE HAR-15-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Responsible Party Noam Y. Harel, MD, PhD, Bronx VA Medical Center
Study Sponsor  ICMJE Bronx VA Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Noam Y. Harel, MD, PhD James J. Peters VA Medical Center
PRS Account Bronx VA Medical Center
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP