We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Brain and Nerve Stimulation for Hand Muscles in Spinal Cord Injury and ALS

This study is currently recruiting participants.
Verified February 2017 by Noam Y. Harel, MD, PhD, Bronx VA Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02469675
First Posted: June 11, 2015
Last Update Posted: February 24, 2017
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.
Information provided by (Responsible Party):
Noam Y. Harel, MD, PhD, Bronx VA Medical Center
  Purpose

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.


Condition Intervention
Spinal Cord Injury (SCI) Amyotrophic Lateral Sclerosis (ALS) Device: Transcranial magnetic stimulation Device: Median nerve stimulation Device: Cervical transcutaneous stimulation

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Paired Stimulation to Increase Cortical Transmission to Hand Muscles: Pilot Study

Resource links provided by NLM:


Further study details as provided by Noam Y. Harel, MD, PhD, Bronx VA Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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. ]

Estimated Enrollment: 30
Study Start Date: June 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: TMS only
Transcranial magnetic stimulation over hand motor cortex
Device: Transcranial magnetic stimulation
One TMS pulse every 10 seconds for 20 minutes
Other Name: MagPro R30
Placebo Comparator: Cervical electrical stimulation only
Surface electrical stimulation over cervical spinal cord
Device: Cervical transcutaneous stimulation
One cervical pulse every 10 seconds for 20 minutes
Other Name: Digitimer DS7A
Placebo Comparator: Median nerve electrical stimulation only
Surface electrical stimulation over median nerve at the wrist
Device: Median nerve stimulation
One median nerve pulse every 10 seconds for 20 minutes
Other Name: Digitimer DS7A
Experimental: TMS before cervical stimulation
Transcranial magnetic stimulation paired with cervical electrical stimulation so that TMS signal arrives before electrical signal
Device: Transcranial magnetic stimulation
One TMS pulse every 10 seconds for 20 minutes
Other Name: MagPro R30
Device: Cervical transcutaneous stimulation
One cervical pulse every 10 seconds for 20 minutes
Other Name: Digitimer DS7A
Active Comparator: TMS after cervical stimulation
Transcranial magnetic stimulation paired with cervical electrical stimulation so that TMS signal arrives after electrical signal
Device: Transcranial magnetic stimulation
One TMS pulse every 10 seconds for 20 minutes
Other Name: MagPro R30
Device: Cervical transcutaneous stimulation
One cervical pulse every 10 seconds for 20 minutes
Other Name: Digitimer DS7A
Experimental: TMS before median stimulation
Transcranial magnetic stimulation paired with median nerve electrical stimulation so that TMS signal arrives before electrical signal
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
Active Comparator: TMS after median stimulation
Transcranial magnetic stimulation paired with median nerve electrical stimulation so that TMS signal arrives after electrical signal
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
Experimental: Baseline Testing
Baseline tests of responses to electrical and magnetic stimulation, including different configurations of cervical electrical stimulation.
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

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.

  Eligibility

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)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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): NCT02469675


Contacts
Contact: Tiffany M Santiago, BS (718) 584-9000 ext 3123 tiffany.santiago@va.gov
Contact: Noam Y. Harel, MD, PhD 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: Noam Y Harel, MD PhD    718-584-9000 ext 3123    noam.harel@va.gov   
Sponsors and Collaborators
Bronx VA Medical Center
Investigators
Principal Investigator: Noam Y. Harel, MD, PhD James J. Peters VA Medical Center
  More Information

Responsible Party: Noam Y. Harel, MD, PhD, Staff Physician, Bronx VA Medical Center
ClinicalTrials.gov Identifier: NCT02469675     History of Changes
Other Study ID Numbers: HAR-15-001
First Submitted: June 9, 2015
First Posted: June 11, 2015
Last Update Posted: February 24, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
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.

Keywords provided by Noam Y. Harel, MD, PhD, Bronx VA Medical Center:
Spinal Cord Injuries
Amyotrophic Lateral Sclerosis
Transcranial magnetic stimulation, single pulse
non-invasive brain stimulation

Additional relevant MeSH terms:
Wounds and Injuries
Sclerosis
Spinal Cord Injuries
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Neurodegenerative Diseases
Neuromuscular Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases