Monoaminergic Modulation of Motor Function in Subacute Incomplete Spinal Cord Injury (SCI)
Status:
Unknown status
Trial end date:
2020-07-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 1
Details
Lead Sponsor:
Rehabilitation Institute of Chicago Shirley Ryan AbilityLab