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Interactions Between Neurostimulation and Physical Exercise

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ClinicalTrials.gov Identifier: NCT03076632
Recruitment Status : Withdrawn (Funding obtained to conduct expanded study - to be posted to ClinicalTrials.gov.)
First Posted : March 10, 2017
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Noam Y. Harel, MD, PhD, Bronx VA Medical Center

Brief Summary:
  • People with cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) have reduced connections in the nerve circuits between the brain and the hands. Activating spared nerve circuits is one potential way to improve recovery.
  • The investigators are testing different combinations of physical wrist and hand movements paired with magnetic brain stimulation and electrical spinal cord or nerve stimulation to see the effects on nerve transmission to hand muscles.
  • This is a preliminary study. This study is testing for temporary changes in nerve transmission to hand muscles. There is no expectation of long-term benefit from this study. If temporary changes are seen in this study, then future studies would focus on how to prolong that effect.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Amyotrophic Lateral Sclerosis Device: Cervical plus transcranial stimulation Device: Cervical stimulation plus hand/wrist exercise Device: Electromyographic (EMG)-triggered (closed-loop) stimulation Not Applicable

Detailed Description:

Spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) result in a mixture of destroyed, damaged, and spared neural circuits. Activating spared nerve circuits augments neural transmission.

With this goal in mind, the investigators recently developed a novel method of cervical electrical stimulation (CES) to noninvasively activate arm and hand muscles. The investigators are conducting a pilot clinical study (NCT02469675) to establish CES safety in subjects with cervical SCI, ALS, and non-disabled volunteers. To date, 19 subjects have undergone >120 CES sessions without major safety or tolerability issues.

The current study is designed to gain further mechanistic insight. In Aim 1, the investigators will test in more detail how CES (traveling through spinal and peripheral circuits) interacts with individual pulses of TMS (traveling through corticospinal circuits). In Aim 2, the investigators will further test CES's therapeutic potential by combining stimulation with simultaneous physical exercises. In Aim 3, the investigators will compare the acute effects on synaptic transmission of passive stimulation to stimulation triggered by the subject's own muscle activity.

Please note, this is a preliminary study. This study is testing for temporary changes in nerve transmission to hand muscles. There is no expectation of long-term benefit from this study. If the investigators see temporary changes in this study, then future studies would focus on how to prolong that effect.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Each subject will receive combinations of brain stimulation, cervical stimulation, or peripheral nerve stimulation, either with or without performing simultaneous hand exercises.
Masking: Single (Outcomes Assessor)
Masking Description: Raw electromyography data assessed while masked to specific conditions.
Primary Purpose: Device Feasibility
Official Title: Acute Interactions Between Electromagnetic Stimulation and Physical Exercise
Estimated Study Start Date : April 1, 2017
Actual Primary Completion Date : September 26, 2017
Estimated Study Completion Date : September 26, 2017


Arm Intervention/treatment
Active Comparator: Non-disabled volunteers

Volunteers without neurological injury.

Interventions:

  • Cervical plus transcranial stimulation
  • Cervical stimulation plus hand/wrist exercise
  • Electromyographic (EMG)-triggered (closed-loop) stimulation
Device: Cervical plus transcranial stimulation
Conditioning pulses of cervical electrical stimulation will be delivered before or after test pulses of transcranial magnetic stimulation.

Device: Cervical stimulation plus hand/wrist exercise
Pulses of cervical stimulation will be delivered while the subject performs finger and wrist motor tasks.

Device: Electromyographic (EMG)-triggered (closed-loop) stimulation
Force and EMG activity of specific hand muscles will be used to trigger peripheral nerve electrical stimulation or transcranial magnetic stimulation.

Active Comparator: Spinal cord injury

Volunteers with motor-incomplete cervical spinal cord injury.

Interventions:

  • Cervical plus transcranial stimulation
  • Cervical stimulation plus hand/wrist exercise
  • Electromyographic (EMG)-triggered (closed-loop) stimulation
Device: Cervical plus transcranial stimulation
Conditioning pulses of cervical electrical stimulation will be delivered before or after test pulses of transcranial magnetic stimulation.

Device: Cervical stimulation plus hand/wrist exercise
Pulses of cervical stimulation will be delivered while the subject performs finger and wrist motor tasks.

Device: Electromyographic (EMG)-triggered (closed-loop) stimulation
Force and EMG activity of specific hand muscles will be used to trigger peripheral nerve electrical stimulation or transcranial magnetic stimulation.

Active Comparator: Amyotrophic lateral sclerosis

Volunteers with amyotrophic lateral sclerosis.

Interventions:

  • Cervical plus transcranial stimulation
  • Cervical stimulation plus hand/wrist exercise
  • Electromyographic (EMG)-triggered (closed-loop) stimulation
Device: Cervical plus transcranial stimulation
Conditioning pulses of cervical electrical stimulation will be delivered before or after test pulses of transcranial magnetic stimulation.

Device: Cervical stimulation plus hand/wrist exercise
Pulses of cervical stimulation will be delivered while the subject performs finger and wrist motor tasks.

Device: Electromyographic (EMG)-triggered (closed-loop) stimulation
Force and EMG activity of specific hand muscles will be used to trigger peripheral nerve electrical stimulation or transcranial magnetic stimulation.




Primary Outcome Measures :
  1. Motor evoked potentials (MEP) [ Time Frame: Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks. ]
    Change in MEP amplitude of hand and wrist muscles in response to conditioned versus unconditioned pulses of TMS

  2. Volitional electromyographic (EMG) activity [ Time Frame: Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks. ]
    Change in EMG activity of hand and wrist muscles in response to cervical stimulation during physical activity

  3. Response to closed-loop stimulation [ Time Frame: Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks. ]
    Transmission of pulses of TMS or peripheral nerve stimulation will be increased when stimulation is triggered by endogenous EMG activity.



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

Inclusion Criteria:

  1. Age between 21 and 65 years;
  2. Chronic (more than 12 months since injury) incomplete SCI between levels C2-C8 or diagnosis of definite or probable ALS;
  3. Incomplete weakness of left or right hand muscles: score of 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction;
  4. Detectable F-wave responses of the left or right abductor pollicis brevis muscle to median nerve stimulation.

Exclusion Criteria:

  1. Multiple spinal cord lesions;
  2. History of seizures;
  3. Ventilator dependence or patent tracheostomy site;
  4. Use of medications that significantly lower seizure threshold, such as tricyclic antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion;
  5. History of stroke, brain tumor, brain abscess, or multiple sclerosis;
  6. History of moderate or 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);
  7. History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants, or cardiac pacemaker/defibrillator;
  8. Significant coronary artery or cardiac conduction disease;
  9. Recent history (within past 6 months) of recurrent autonomic dysreflexia, defined as a syndrome of sudden rise in systolic pressure greater than 20 mm Hg or diastolic pressure greater than 10 mm Hg, without rise in heart rate, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (this will be closely monitored during all screening and testing procedures);
  10. History of bipolar disorder;
  11. History of suicide attempt;
  12. Active psychosis;
  13. Heavy alcohol consumption (greater than equivalent of 5 oz of liquor) within previous 48 hours;
  14. Open skin lesions over the face, neck, shoulders, or arms;
  15. Pregnancy
  16. 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): NCT03076632


Sponsors and Collaborators
Bronx VA Medical Center
Investigators
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Principal Investigator: Noam Y. Harel, MD, PhD James J. Peters VAMC

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Responsible Party: Noam Y. Harel, MD, PhD, Staff Physician, Bronx VA Medical Center
ClinicalTrials.gov Identifier: NCT03076632     History of Changes
Other Study ID Numbers: HAR-16-042
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Noam Y. Harel, MD, PhD, Bronx VA Medical Center:
transcranial magnetic stimulation
neurostimulation
non-invasive stimulation
closed-loop stimulation
Additional relevant MeSH terms:
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Spinal Cord Injuries
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Neurodegenerative Diseases
Neuromuscular Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases