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Non-invasive Cervical Electrical Stimulation for SCI

Non-invasive Cervical Electrical Stimulation for SCI

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03414424
Enrollment
30
Registered
2018-01-30
Start date
2017-08-22
Completion date
2021-04-30
Last updated
2023-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Spinal Cord Injuries

Keywords

transcutaneous electric nerve stimulation, transcranial magnetic stimulation

Brief summary

Most spinal cord injuries (SCI) are anatomically incomplete - some nerve circuits remain intact, even if the individual cannot feel or control them. Activating spared nerve circuits may improve functional recovery. With this goal, the Investigators have developed a form of electrical stimulation over the cervical spinal cord that can activate muscles in both hands simultaneously and comfortably. This technique, called cervical electrical stimulation (CES), works at the skin surface - no surgery or other invasive procedures are required. The long-term goal is to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI. In the current study, the Investigators first need to better understand how CES works. In the first half of this study, the Investigators will take a systematic approach to determining how CES interacts with other circuits in the spinal cord and the brain. In the second half of the study, the Investigators will test combinations of CES with active hand and wrist movements to find ways to enhance physical movement with CES. These experiments will improve understanding of electrical stimulation in SCI, and may set the table for future treatments to prolong any short-term benefits observed in this study.

Detailed description

Roughly 60% of spinal cord injuries occur at the cervical level. Most injuries are anatomically incomplete. Activating spared nerve circuits augments functional recovery of the damaged nervous system. With this goal, the Investigators have developed a novel method of non-invasive cervical electrical stimulation (CES). Preliminary data show that CES triggers afferent sensory or efferent motor nerve roots depending on stimulus intensity, resulting in concurrent activation of multiple muscles on both upper limbs. the Investigators aim to use CES to strengthen residual circuits to hand muscles after SCI. Regaining control over hand function represents the top priority for individuals with cervical SCI. However, much more work needs to be done to better understand underlying CES mechanisms, its interactions with segmental and supraspinal circuits, and its optimal stimulation parameters for improving neural transmission to the hands. This proposal will address these issues. Mechanistic experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with transcranial magnetic stimulation (TMS) or peripheral nerve stimuli at varying intensities, sites, and interstimulus intervals. Mechanistic hypotheses: Conditioning subthreshold CES pulses will potentiate responses to test pulses of TMS and peripheral nerve F-wave stimulation, will reduce responses to test pulses of peripheral nerve H-reflex stimulation, and will modulate response to test suprathreshold CES pulses in either direction depending on conditioning stimulus interval and intensity. These experiments will elucidate CES circuit interactions at both the segmental and supraspinal levels. Combined CES-volitional movement experiments: 15 able-bodied volunteers and 15 subjects with motor-incomplete cervical spinal cord injury will undergo systematic combinations of CES with volitional wrist and hand movements at varying intensity and effort level. Combined CES-volitional movement hypotheses: Conditioning subthreshold CES pulses will facilitate concurrent volitional wrist and hand muscle activation. Suprathreshold CES will transiently inhibit concurrent volitional wrist and hand muscle activation. These experiments will shed light on the clinically relevant possibility of using CES to enhance response to physical exercise therapy. Completion of the proposed studies will characterize CES circuit timing and distribution, and will demonstrate in principle the potential for CES to enhance physical therapy for wrist and hand muscles. Furthermore, this approach is compatible with other interventions, including drug and cell-based treatments.

Interventions

CES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex. This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits.

CES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort. This is an experiment designed to detect momentary changes in muscle function.

Sponsors

Bronx VA Medical Center
Lead SponsorFED

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes

Inclusion criteria

* Age between 18 and 75 years; * Chronic (more than 12 months since injury) incomplete SCI between levels C2-C8. * 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. * US Veteran or non-Veteran

Exclusion criteria

* History of other serious injury or disease of central or peripheral nervous system * History of seizures * Ventilator dependence or patent tracheostomy site * Use of medications that significantly lower seizure threshold * History of head trauma with 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 (millimeters of mercury) 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 or suicide attempt or active psychosis * Heavy alcohol consumption (\> equivalent of 5 ounces 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

Design outcomes

Primary

MeasureTime frameDescription
Electromyographic Responses (Active)up to one dayEffect of cervical electrical stimulation (CES) on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.
Electromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Restup to one dayResponse of the target hand muscle to transcranial magnetic stimulation (delivered at 120% of resting motor threshold) with or without a conditioning cervical electrical stimulator pulse (delivered at 90% of resting motor threshold) timed to arrive at cervical synapses 2 milliseconds after transcranial pulse arrival. Response is expressed as percentage change relative to the response to unconditioned transcranial magnetic stimulation.

Countries

United States

Participant flow

Participants by arm

ArmCount
Able Bodied
All subjects undergo same full protocol, including CES at rest and CES plus active hand or wrist movements. CES at rest: CES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex. This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits. CES plus active hand or wrist movements: CES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort. This is an experiment designed to detect momentary changes in muscle function.
15
Spinal Cord Injured
All subjects undergo same full protocol, including CES at rest and CES plus active hand or wrist movements. CES at rest: CES will be delivered at rest at various intensities, in combination with either electrical stimulation over peripheral nerves or magnetic stimulation over the motor cortex. This is an experiment designed to measure CES interactions with other central and peripheral nerve circuits. CES plus active hand or wrist movements: CES will be delivered while the participant performs specific finger or wrist tasks at different degrees of effort. This is an experiment designed to detect momentary changes in muscle function.
15
Total30

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up01
Overall StudyScreened out after consent02

Baseline characteristics

CharacteristicAble BodiedTotalSpinal Cord Injured
Age, Continuous38.7 years
STANDARD_DEVIATION 15
43.1 years
STANDARD_DEVIATION 15.6
47.5 years
STANDARD_DEVIATION 15.4
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants4 Participants2 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
11 Participants23 Participants12 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants3 Participants1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants2 Participants2 Participants
Race (NIH/OMB)
Black or African American
7 Participants9 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants3 Participants1 Participants
Race (NIH/OMB)
White
6 Participants16 Participants10 Participants
Region of Enrollment
United States
15 participants30 participants15 participants
Sex: Female, Male
Female
3 Participants7 Participants4 Participants
Sex: Female, Male
Male
12 Participants23 Participants11 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 150 / 15
other
Total, other adverse events
7 / 157 / 15
serious
Total, serious adverse events
0 / 150 / 15

Outcome results

Primary

Electromyographic Responses (Active)

Effect of cervical electrical stimulation (CES) on concurrent finger or wrist active movements will be measured via root-mean-square of ongoing muscle activity in various hand and forearm muscles.

Time frame: up to one day

Population: Data collection for this outcome was plagued with technical problems. The relative timing of cervical stimulation relative to active effort was irregularly applied. Grant funding expired.~It is not possible to analyze the data collected for this aim.

Primary

Electromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Rest

Response of the target hand muscle to transcranial magnetic stimulation (delivered at 120% of resting motor threshold) with or without a conditioning cervical electrical stimulator pulse (delivered at 90% of resting motor threshold) timed to arrive at cervical synapses 2 milliseconds after transcranial pulse arrival. Response is expressed as percentage change relative to the response to unconditioned transcranial magnetic stimulation.

Time frame: up to one day

Population: Two enrolled spinal cord injury (SCI) participants failed screening. Data for transcranial magnetic stimulation (TMS) were excluded from two more SCI participants who were found after screening to either have unacceptable electrical background electromyographic activity or unreliable responses in resting muscle during TMS.

ArmMeasureValue (MEAN)Dispersion
Able-bodiedElectromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Rest6.1 % change from unconditioned TMS.Standard Error 8.9
Spinal Cord InjuryElectromyographic Responses to Transcranial Magnetic and Cervical Electrical Stimulation at Rest32.0 % change from unconditioned TMS.Standard Error 27.8

Source: ClinicalTrials.gov · Data processed: Feb 22, 2026