Monoaminergic Modulation of Motor Function in Subacute Incomplete Spinal Cord Injury (SCI)

Summary

The primary goal of the proposed clinical trial is to investigate the combined effects of walking training and monoaminergic agents (SSRIs and TIZ) on motor function of individuals in sub-acute (2-7 mo) human motor incomplete Spinal Cord Injury (SCI), with a primary emphasis on improvement in locomotor capability. We hypothesize that the use of these drugs applied early following SCI may facilitate independent stepping ability, and its combination with intensive stepping training will result in improved locomotor recovery following incomplete SCI. Loss of descending control via norepinephrine inputs following spinal cord injury can impair normal sensorimotor function through depressing motor excitability and impairing walking capacity. Replacing these inputs with drugs can alter the excitability and assist with reorganization of locomotor circuits. Assessment of single-dose administration of these agents has been tested in patients with motor incomplete spinal cord injury; only limited changes in walking performance have been noted. The resultant onset of weakness and increase in involuntary reflexes following motor incomplete SCI may partly be a result of damage to descending pathways to the spinal cord that control the release of serotonin. In models of SCI, for example, application of agents that simulate serotonin has been shown to change voluntary motor behaviors, including improvement of walking recovery. In humans following neurological injury, the effects of 5HT agents are unclear. Few previous reports indicate improved motor function following administration of agents which enhance the available serotonin in the brain, although some data suggests that increased serotonin may be beneficial. In this application, we propose to study the effects of clinically used agents that increase or decrease intrinsic serotonin activity in the brain on strength and walking ability following human motor incomplete SCI. Using detailed electrophysiological recordings, and biomechanical and behavioral measures, we will determine the effects of single or chronic doses of these drugs on voluntary and involuntary motor behaviors during clinical measures and walking measures. The novelty of this proposed research is the expectation that agents that increase serotonin activity may increase abnormal reflexes in SCI, but simultaneously help to facilitate motor and walking recovery. Despite potential improvements in voluntary function, the use of pharmacological agents that may enhance spastic motor behaviors following SCI is in marked contrast to the way in which drugs are typically used in the clinical setting.

Conditions

• Spinal Cord Injury

Interventions

DRUG

Lexapro

Agent + training vs Placebo + training

DRUG

Placebo

Agent + training vs Placebo + training

Sponsors & Collaborators

• Shirley Ryan AbilityLab

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-02-29

Primary Completion

2020-07-31

Completion

2020-07-31

Countries

• United States

Study Locations