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Interactions Between Neurostimulation and Physical Exercise

Primary Purpose

Spinal Cord Injuries, Amyotrophic Lateral Sclerosis

Status

Withdrawn

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Cervical plus transcranial stimulation

Cervical stimulation plus hand/wrist exercise

Electromyographic (EMG)-triggered (closed-loop) stimulation

About this trial

This is an interventional device feasibility trial for Spinal Cord Injuries focused on measuring transcranial magnetic stimulation, neurostimulation, non-invasive stimulation, closed-loop stimulation

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Age between 21 and 65 years;
Chronic (more than 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 2, 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.

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 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);
History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants, or cardiac pacemaker/defibrillator;
Significant coronary artery or cardiac conduction disease;
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);
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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Non-disabled volunteers

Spinal cord injury

Amyotrophic lateral sclerosis

Arm Description

Volunteers without neurological injury. Interventions: Cervical plus transcranial stimulation Cervical stimulation plus hand/wrist exercise Electromyographic (EMG)-triggered (closed-loop) stimulation

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

Volunteers with amyotrophic lateral sclerosis. Interventions: Cervical plus transcranial stimulation Cervical stimulation plus hand/wrist exercise Electromyographic (EMG)-triggered (closed-loop) stimulation

Outcomes

Primary Outcome Measures

Motor evoked potentials (MEP)

Change in MEP amplitude of hand and wrist muscles in response to conditioned versus unconditioned pulses of TMS

Volitional electromyographic (EMG) activity

Change in EMG activity of hand and wrist muscles in response to cervical stimulation during physical activity

Response to closed-loop stimulation

Transmission of pulses of TMS or peripheral nerve stimulation will be increased when stimulation is triggered by endogenous EMG activity.

Secondary Outcome Measures

Full Information

NCT ID

NCT03076632

First Posted

February 23, 2017

Last Updated

September 26, 2017

Sponsor

Bronx VA Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03076632

Brief Title

Interactions Between Neurostimulation and Physical Exercise

Official Title

Acute Interactions Between Electromagnetic Stimulation and Physical Exercise

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Funding obtained to conduct expanded study - to be posted to ClinicalTrials.gov.

Study Start Date

April 1, 2017 (Anticipated)

Primary Completion Date

September 26, 2017 (Actual)

Study Completion Date

September 26, 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Bronx VA Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Cord Injuries, Amyotrophic Lateral Sclerosis

Keywords

transcranial magnetic stimulation, neurostimulation, non-invasive stimulation, closed-loop stimulation

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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

Outcomes Assessor

Masking Description

Raw electromyography data assessed while masked to specific conditions.

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Non-disabled volunteers

Arm Type

Active Comparator

Arm Description

Volunteers without neurological injury. Interventions: Cervical plus transcranial stimulation Cervical stimulation plus hand/wrist exercise Electromyographic (EMG)-triggered (closed-loop) stimulation

Arm Title

Spinal cord injury

Arm Type

Active Comparator

Arm Description

Arm Title

Amyotrophic lateral sclerosis

Arm Type

Active Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

Cervical plus transcranial stimulation

Intervention Description

Conditioning pulses of cervical electrical stimulation will be delivered before or after test pulses of transcranial magnetic stimulation.

Intervention Type

Device

Intervention Name(s)

Cervical stimulation plus hand/wrist exercise

Intervention Description

Pulses of cervical stimulation will be delivered while the subject performs finger and wrist motor tasks.

Intervention Type

Device

Intervention Name(s)

Electromyographic (EMG)-triggered (closed-loop) stimulation

Intervention Description

Force and EMG activity of specific hand muscles will be used to trigger peripheral nerve electrical stimulation or transcranial magnetic stimulation.

Primary Outcome Measure Information:

Title

Motor evoked potentials (MEP)

Description

Change in MEP amplitude of hand and wrist muscles in response to conditioned versus unconditioned pulses of TMS

Time Frame

Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks.

Title

Volitional electromyographic (EMG) activity

Description

Change in EMG activity of hand and wrist muscles in response to cervical stimulation during physical activity

Time Frame

Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks.

Title

Response to closed-loop stimulation

Description

Transmission of pulses of TMS or peripheral nerve stimulation will be increased when stimulation is triggered by endogenous EMG activity.

Time Frame

Four visits (3 for non-disabled volunteers) taking place over 2 to 6 weeks.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age between 21 and 65 years; Chronic (more than 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 2, 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. 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 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); History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants, or cardiac pacemaker/defibrillator; Significant coronary artery or cardiac conduction disease; 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); 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Noam Y. Harel, MD, PhD

Organizational Affiliation

James J. Peters VAMC

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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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Interactions Between Neurostimulation and Physical Exercise

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