Effects of Zolmitriptan on Sensory Transmission After Spinal Cord Injury

Sponsor

University of Alberta (Other)

Overall Status

Completed

CT.gov ID

NCT01587170

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries Muscle Spasticity

Study Design

Study Type:

Observational

Actual Enrollment :

13 participants

Official Title:

Phase 2: Effects of Zolmitriptan on Sensory Afferent Transmission After Spinal Cord Injury

Study Start Date :

Jan 1, 2012

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Uninjured control subjects Uninjured, control subjects who are not taking any of the contraindicated drugs.
Spinal-cord injured subjects Patients who have suffered a spinal cord injury (>1year ago).

Outcome Measures

Primary Outcome Measures

Change in H-reflex amplitude from baseline [Pre baseline, 30, 60, 90 and 120 minutes]
H-reflexes in the soleus muscle will be evoked by stimulation of the posterior tibial nerve. The response will recorded before drug intake, and every 30 minutes after drug intake up to 2 hours to determine the change in the response as a result of drug intake.
Change in Cutaneomuscular Reflex Responses from baseline [Pre baseline, 30, 60, 90, 120 minutes]
Tibialis anterior reflex responses will be recorded after medial arch stimulation of the foot. Recordings will be taken to provide a pre-drug baseline and then every 30 minutes after drug intake up to 2 hrs to determine the change in these reflex responses after drug intake.

Secondary Outcome Measures

Change in Blood pressure [Pre and 60min, 120min post drug]
Blood pressure will be measured to determine the safety of the drug during the study.
Change in Heart rate [Predrug, 60min and 120min after drug]
Heart rate will be monitored before drug intake and 60 and 120 min after drug intake so as to monitor vital signs.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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