Maximizing Spike - Timing Dependent Plasticity After Spinal Cord Injury

Enhancing STDP After Spinal Cord Injury

Sponsors

Lead sponsor: VA Office of Research and Development

Collaborator: University of Miami

Source VA Office of Research and Development
Brief Summary

The overall goal is to develop new clinical approaches to restore upper-limb function after incomplete cervical spinal cord injury (SCI). Corticospinal tract (CST) axons are involved in controlling upper-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 upper-limb function in humans with incomplete cervical SCI. Motor training will be combined with paired-pulse STDP stimulation to further enhance plasticity and behavioral recovery.

Overall Status Active, not recruiting
Start Date December 15, 2017
Completion Date December 12, 2021
Primary Completion Date January 1, 2021
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Changes in amplitude of Motor evoked potential size post treatment at minute 0, minute 10, minute30, minute 60.
Enrollment 500
Condition
Intervention

Intervention type: Drug

Intervention name: Seromycin

Description: 100mg pill of Seromycin by mouth will be administered

Intervention type: Device

Intervention name: STDP

Description: noninvasive magnetic or electrical stimulation will be applied to the brain

Intervention type: Other

Intervention name: Training

Description: following the directions of the researcher the participant will be asked to perform specific repetitive movements using their hand, arm or leg .

Intervention type: Drug

Intervention name: Dextromethorphan

Description: 150mg of DExtromethorphan pill will be administered

Arm group label: STDP+Dextromethorphan/ Placebo

Intervention type: Drug

Intervention name: Seromycin Placebo

Description: placebo pill will be administered

Arm group label: STDP+ Seromycin/ Placebo

Intervention type: Drug

Intervention name: Dextromethorphan Placebo

Description: placebo pill will be administered

Arm group label: STDP+Dextromethorphan/ Placebo

Intervention type: Device

Intervention name: Sham STDP

Description: noninvasive magnetic or electrical sham stimulation will be applied to the brain

Arm group label: Sham STDP

Eligibility

Criteria:

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 ( 2 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.

Gender: All

Minimum age: 18 Years

Maximum age: 85 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Martin Oudega, PhD Principal Investigator Edward Hines Jr. VA Hospital, Hines, IL
Location
facility
Miami VA Healthcare System, Miami, FL
Edward Hines Jr. VA Hospital, Hines, IL
Location Countries

United States

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 7
Arm Group

Arm group label: STDP

Arm group type: Active Comparator

Description: paired stimulation will be given to the brain so that the messages are received at the spinal cord at the correct time.

Arm group label: STDP+ Seromycin/ Placebo

Arm group type: Active Comparator

Description: a single dose of 100mg of Seromycin will be given in a pill form by mouth and then paired stimulation will be applied to the brain so that the messages are received at the spinal cord at the correct time.

Arm group label: STDP+Dextromethorphan/ Placebo

Arm group type: Active Comparator

Description: a single dose of 150mg of Dextromethorphan will be given in a pill form by mouth and then paired stimulation (STDP) will be applied to the brain so that the messages are received at the spinal cord at the correct time.

Arm group label: Training +STDP

Arm group type: Active Comparator

Description: motor training exercises will be done repetitively and then stimulation (STDP) to the brain will be applied.

Arm group label: Training

Arm group type: Active Comparator

Description: motor training exercises will be done repetitively

Arm group label: Training + Seromycin+STDP/ Sham STDP

Arm group type: Active Comparator

Description: Motor Training will be completed, then a single dose of 100 mg of Seromycin will be administered in pill form, and then stimulation or sham stimulation will be applied to the brain

Arm group label: Sham STDP

Arm group type: Active Comparator

Description: fake stimulation will be given to the brain so that the messages are received at the spinal cord at the correct time.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Intervention model description: Magnetic Stimulation and electrical stimulation

Primary purpose: Treatment

Masking: Single (Participant)

Masking description: participants will not know if they receive real or sham stimulation

Source: ClinicalTrials.gov