Enhancing STDP After Spinal Cord Injury

VA Office of Research and Development

Status: Completed

Conditions: Spinal Cord Injury

Treatments: Other: STDP; Other: Multisite-STDP; Behavioral: Training; Other: Sham STDP

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT02701777

B1807-R

Details and patient eligibility

About

The overall goal is to develop new clinical approaches to restore limb function after spinal cord injury (SCI). Corticospinal tract (CST) axons are involved in controlling limb function. Paired pulse induced spike-timing dependent plasticity (STDP) enhances synaptic strength between residual CST axons and spinal motoneurons (SMNs) resulting in temporary improvements in limb function in humans with incomplete SCI. Motor training will be combined with paired-pulse STDP stimulation to further enhance plasticity and behavioral recovery.

Full description

To induce STDP with paired pulse, corticospinal volleys evoked by either transcranial magnetic stimulation over the primary motor cortex for upper extremities or electrical stimulation over the thoracic spine for lower extremities arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles, 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of corresponding peripheral nerves.

Enrollment: 62 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Participants who are unimpaired healthy controls:

• Male and females between ages 18-85 years
• Right handed
• Able to complete precision grips with both hands
• Able to complete full wrist flexion-extension bilaterally
• Able to walk unassisted
• Able to complete full ankle flexion-extension bilaterally

Participants who have had a spinal cord injury:

• Male and females between ages 18-85 years
• SCI ( 6 months of injury)
• Spinal Cord injury at or above L5
• The ability to produce a visible precision grip force with one hand
• Able to perform some small wrist flexion and extension
• The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles
• No subjects will be excluded based on their race, religion, ethnicity, gender or HIV status.
• ASIA A,B,C, or D

Exclusion criteria

Exclusion criteria for enrollment For SCI and Healthy Control Subjects (4-8 exclusion for non-invasive brain stimulation only):

• Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
• Any debilitating disease prior to the SCI that caused exercise intolerance
• Premorbid, ongoing major depression or psychosis, altered cognitive status
• History of head injury or stroke
• Metal plate in skull
• History of seizures
• Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2)
• Pregnant females
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
• Individuals with scalp shrapnel, cochlear implants, or aneurysm clips.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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62 participants in 4 patient groups

STDP

Active Comparator group

Description:

Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time.

Treatment:

Other: STDP

STDP + Training

Active Comparator group

Description:

Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time. Motor training will follow paired stimulation.

Treatment:

Behavioral: Training

Other: STDP

Sham STDP + Training

Active Comparator group

Description:

Sham or fake paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined times. Motor training will follow stimulation.

Treatment:

Behavioral: Training

Other: Sham STDP

Multisite-STDP + Training

Other group

Description:

Prospective Single Cohort Multisite-Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time. Motor training will follow paired stimulation.

Treatment:

Behavioral: Training

Other: Multisite-STDP