Clinical trial NCT01587170: Effects of Zolmitriptan on Sensory Transmission After Spinal Cord Injury
Official title: Phase 2: Effects of Zolmitriptan on Sensory Afferent Transmission After Spinal Cord Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spinal Cord Injuries
Muscle Spasticity
Keywords: spasticity
spinal cord injury
zolmitriptan
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2012-04-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Spinal cord injury subjects

Brief summary: After spinal cord injury, patients develop a spastic syndrome that is characterized by hyperactive reflexes, increased muscle tone, clonus and involuntary muscle spasms. The neuronal mechanisms behind the development of spasticity remain largely unknown, though animal experiments have shown that changes occur both at the level of the motoneuron and sensory neurons. This project aims to examine the changes that occur in the modulation of sensory afferent transmission after spinal cord injury, and how these changes can contribute to the triggering and initiation of muscle spasms after chronic spinal cord injury in humans.

It is known that after spinal cord injury, the majority of descending sources of monoamines, such as serotonin (5HT), are abolished. Animal experiments have shown that 5HT receptors on sensory neurons in the spinal cord are responsible for inhibiting sensory transmission. As a result, after spinal cord injury these receptors are no longer activated below an injury, resulting in the production of large, long excitatory responses in the motoneuron when sensory are activated. This large sensory activation of the motoneuron can, in turn, activate a long response in the motoneuron to produce an involuntary muscle spasm. The aim of our study is to determine whether, similar to animal experiments, the 5HT1 receptors are responsible for sensory inhibition in spinal cord injured subjects, and whether activating these receptors (through the 5HT1 agonist Zolmitriptan) will restore the normal inhibition of sensory transmission that is lost after injury, thereby resulting in a decrease in the initiation of involuntary muscle spasms.


Eligibility criteria: Inclusion Criteria:

* Patients must have suffered a trauma to the spinal cord at least 1 year prior. In addition, subjects must exhibit some degree of spasticity as determined by having an Ashworth Spasticity Score greater than 1 in the ankle or knee.

Exclusion Criteria:

* If patients have damage to the nervous system other than to the spinal cord
* Pregnant women
* Elderly Patients (\> 65 years)
* Alcoholic Patients
* History of ischemic cardiac, cerebrovascular or peripheral vascular syndromes
* Valvular heart disease or cardiac arrhythmias
* Other significant underlying cardiovascular disease (atherosclerotic disease, congenital heart disease)
* Uncontrolled or severe hypertension
* Hemiplegic, basilar or ophthalmologic migraine
* Hypersensitivity to Zolmitriptan or any component of the formulation
* History of Autonomic Dysreflexia
* Patients taking:
* Ergot-containing drugs
* Other 5HT1 Agonists
* MAO Inhibitors
* Cimetidine and other 1A2 Inhibitors
* Propranolol
* Selective Serotonin and Norepinephrine Reuptake Inhibitors
* Acetaminophen
* Metoclopramide
* Xylometazoline
* Oral Contraceptives

Primary outcomes:
measure: Change in H-reflex amplitude from baseline
timeFrame: Pre baseline, 30, 60, 90 and 120 minutes
measure: Change in Cutaneomuscular Reflex Responses from baseline
timeFrame: Pre baseline, 30, 60, 90, 120 minutes
Secondary outcomes:
measure: Change in Blood pressure
timeFrame: Pre and 60min, 120min post drug
measure: Change in Heart rate
timeFrame: Predrug, 60min and 120min after drug
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Monica A Gorassini, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Ming Chan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murray KC, Stephens MJ, Rank M, D'Amico J, Gorassini MA, Bennett DJ. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors. J Neurophysiol. 2011 Aug;106(2):925-43. doi: 10.1152/jn.01011.2010. Epub 2011 Jun 8.