Cyproheptadine and Chlorpromazine Effects on Spasticity
The main goal of this research is to understand the neuronal mechanisms that mediate the development of spasticity and motor dysfunction after spinal cord injury. The investigators examine how neurons and neuronal circuits in an injured nervous system adapt to produce the uncontrolled and unwanted muscle contractions that affect the majority (80%) of patients with spinal cord injury. One of the neurons that the investigators study is the motoneuron that excites the muscles of the limbs to produce movement. Previously, the investigators have shown that after spinal cord injury, the excessive and uncontrolled activity of motoneurons during muscle spasms is mediated, in large part, by the activation of calcium currents in the human motoneuron. In human patients the investigators have used recordings from single muscle fibres to estimate the contribution of these calcium currents in activating the motoneuron during muscle spasms. In this proposal, the investigators study why motoneurons recover these calcium currents and self-sustained activity after chronic spinal cord injury. Because the calcium currents require the presence of the monoamine serotonin (5HT) to activate, and this monoamine is greatly reduced after injury, the investigators examine if the calcium currents recover because the 5HT receptors become spontaneously active without the need for 5HT to bind to the receptor, which the investigators hypothesize to be one of the causes of spasticity after spinal cord injury. This research will pave the way to develop new pharmacological and rehabilitative therapies to both control spasticity after spinal cord injury and augment residual motor movements.
Spinal Cord Injuries
|Official Title:||Phase 3 Study of Cyproheptadine and Chlorpromazine Effects on Spasticity After Spinal Cord Injury|
- Cutaneomuscular Reflex Responses [ Time Frame: Change after drug intake at baseline, 30minutes, 60minutes, 90minutes and 120minutes ] [ Designated as safety issue: No ]Tibialis anterior reflex responses evoked by stimulation of the medial arch of the foot will be measured before and after drug administration.
- Paired motor unit recordings [ Time Frame: Change at baseline and 30, 60, 90 and 120min after drug intake ] [ Designated as safety issue: No ]We obtain paired motor unit recordings to determine changes in neuronal excitability after drug intake in incomplete spinal-cord injured subjects only.
- Blood pressure and Heart rate [ Time Frame: Change at baseline and 30, 60, 90, 120 minutes after drug intake ] [ Designated as safety issue: Yes ]We measure blood pressure and heart rate to determine the safety of the drug during the experiment and whether we can continue safely.
|Study Start Date:||July 2010|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Complete Spinal Cord Injured Subjects
Patients with no motor scores in their legs and suffering a complete spinal cord injury.
Incomplete Spinal Cord Injured Subjects
Patient with some motor preservation below the injury and suffering an incomplete spinal cord injury.