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Effects of Zolmitriptan on Sensory Transmission After Spinal Cord Injury

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Alberta
ClinicalTrials.gov Identifier:
NCT01587170
First received: April 23, 2012
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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
Spinal Cord Injuries
Muscle Spasticity

Study Type: Observational
Official Title: Phase 2: Effects of Zolmitriptan on Sensory Afferent Transmission After Spinal Cord Injury

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Change in H-reflex amplitude from baseline [ Time Frame: Pre baseline, 30, 60, 90 and 120 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre baseline, 30, 60, 90, 120 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre and 60min, 120min post drug ] [ Designated as safety issue: No ]
    Blood pressure will be measured to determine the safety of the drug during the study.

  • Change in Heart rate [ Time Frame: Predrug, 60min and 120min after drug ] [ Designated as safety issue: No ]
    Heart rate will be monitored before drug intake and 60 and 120 min after drug intake so as to monitor vital signs.


Enrollment: 13
Study Start Date: January 2012
Study Completion Date: November 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Spinal cord injury subjects

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01587170

Locations
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada
Sponsors and Collaborators
University of Alberta
Investigators
Principal Investigator: Monica A Gorassini, PhD University of Alberta
Principal Investigator: Ming Chan, MD, PhD University of Alberta
  More Information

Additional Information:
Publications:
Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT01587170     History of Changes
Other Study ID Numbers: Pro00019967
Study First Received: April 23, 2012
Last Updated: November 30, 2012
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University of Alberta:
spasticity
spinal cord injury
zolmitriptan

Additional relevant MeSH terms:
Muscle Hypertonia
Muscle Spasticity
Spinal Cord Injuries
Central Nervous System Diseases
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Spinal Cord Diseases
Trauma, Nervous System
Wounds and Injuries
Zolmitriptan
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Serotonin 5-HT1 Receptor Agonists
Serotonin Agents
Serotonin Receptor Agonists

ClinicalTrials.gov processed this record on November 24, 2014