Lower Limb Function After Spinal Cord Injury

Phase 4

Completed

• Conditions: Spinal Cord Injury
• Interventions: Drug: D-Cycloserine; Drug: Placebo; Other: Training; Other: Stimulation; Other: Placebo Stimulation

• Registration Number: NCT02635893
• Lead Sponsor: Shirley Ryan AbilityLab

Brief Summary

This is a randomized, experimental study that examines the physiology of central nervous system pathways contributing to the control of bilateral movements in individuals with spinal cord injuries and promotes the recovery of lower-limb motor function through the use of stimulation and locomotor training.

Detailed Description

This study plans to examine plasticity in corticospinal synapses of lower-limb muscles. it has been demonstrated that plasticity elicited at corticospinal synapses in the spinal cord result in enhancements in electromyographic (EMG) and force activity in upper-limb muscles. The first step in this proposal is to determine if synaptic plasticity can be elicited in corticospinal projections targeting lower-limb muscles in humans with SCI.

We will also study methods to strengthen corticospinal plasticity to promote recovery of leg clearance during training. We will use two novel strategies to enhance plasticity in corticospinal synapses of lower-limb muscles after SCI: a). administration of an N-methyl-D-aspartate (NMDA) receptor agonist (i.e. D-cycloserine), and b). Combine NMDA-induced corticospinal plasticity with training (2D lower limb training and locomotor training. Corticospinal synaptic plasticity is thought to depend on activation of NMDA receptors and D-cycloserine enhances motor skill behaviors in animals and humans will be enhanced by NMDA-induced corticospinal plasticity. An important strength of this aim is the combination of training and strategies that aimed at enhancing the synaptic efficacy of residual corticospinal projections. Training effects on physiological pathways will be explored and correlated with locomotor function

Study Timeline

• Study First Submitted: 2015-12-11
• Study First Submitted QC: 2015-12-16
• Study First Posted: 2015-12-21
• Study Start: 2019-06-21
• Primary Completion: 2021-03-09
• Study Completion: 2021-04-11
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-29
• Last Update Posted: 2021-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 257

Inclusion Criteria

• 4. Inclusion criteria for individuals with SCI:
  • Male and females between ages 18-85 years of age
  • SCI ( ≥1 month of injury)
  • ASIA A, B,C and D
  • SCI above L5
  • Able to perform a visible contraction with dorsiflexor and hip flexor muscles (allowing testing of largely impaired patients)
  • Able to ambulate a few steps with or without an assistive device

Inclusion criteria for healthy controls:

• Male and females between ages 18-85 years of age
• Able to walk and complete lower-limb tests with both legs

Exclusion Criteria

Exclusion criteria for individuals with SCI

• 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 such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants.
• Pregnant females, and
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida or herniated cervical disk.

Exclusion criteria for healthy controls:

• Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease,
• Any debilitating disease that causes 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 such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants.
• Pregnant females, and
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida or herniated cervical disk.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
D-Cycloserine/Placebo + Stimulation	Stimulation	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation.
Training+Med/Placebo+Stimulation	Placebo	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation followed by training.
Training+Med/Placebo+Stimulation	Stimulation	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation followed by training.
Training+Med+Stimulation/Placebo Stim	Stimulation	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation or placebo stimulation followed by training.
Training+Med+Stimulation/Placebo Stim	Training	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation or placebo stimulation followed by training.
Training+Med/Placebo+Stimulation	Training	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation followed by training.
D-Cycloserine/Placebo + Stimulation	Placebo	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation.
Training+Med+Stimulation/Placebo Stim	Placebo Stimulation	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation or placebo stimulation followed by training.
D-Cycloserine/Placebo + Stimulation	D-Cycloserine	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation.
Training+Med/Placebo+Stimulation	D-Cycloserine	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation followed by training.
Training+Med+Stimulation/Placebo Stim	D-Cycloserine	Participant will be given a single dose of 100 mg of D-Cycloserine or placebo before receiving stimulation or placebo stimulation followed by training.

Primary Outcome Measures

Name	Time	Method
Changes in motor evoked potential size	30 minutes before and 30 minutes after intervention

Trial Locations

Locations (1)

The Shirley Ryan Ability Lab; 🇺🇸 Chicago, Illinois, United States