Pilot, Proof-of-Concept Study of Sublingual Tizanidine in Children With Chronic Traumatic Brain Injury (TBI)

This study has been completed.
Sponsor:
Information provided by:
Teva GTC
ClinicalTrials.gov Identifier:
NCT00287157
First received: February 2, 2006
Last updated: January 20, 2009
Last verified: September 2007
  Purpose

Nightly administration of a unique, sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve sleep and next-day functioning in CP (cerebral palsy) patients. It is hypothesized that this improvement in sleep efficiency (i.e.,fewer wake episodes, longer time asleep, etc.) with resulting improvement in quality-of-life (i.e.,improvements in next-day functioning, cognition and movement) may also be seen in a similar patient population, i.e., children with traumatic brain injury (TBI).


Condition Intervention Phase
Traumatic Brain Injury
Drug: Sublingual Tizanidine HCl
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Two-Way Crossover, Comparative Study to Evaluate the Clinical Efficacy and Safety of Novel Sublingual Tizanidine HCl Versus Placebo in Children With Chronic Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Teva GTC:

Primary Outcome Measures:
  • Improvement in Spasticity, Cognition and Daily Function [ Time Frame: 4 weeks ]

Secondary Outcome Measures:
  • Improvement in nighttime actigraphy sleep parameters [ Time Frame: 4 weeks ]

Enrollment: 5
Study Start Date: December 2006
Study Completion Date: May 2007
Detailed Description:

Sublingual tizanidine, a novel test formulation of the known effective antispasticity agent, has been shown to have a unique pharmacokinetic profile [(i.e., nearly twice the bioavailability/AUC), but with little or no increase in peak plasma levels (Cmax), as compared to oral tizanidine (Zanaflex)]. When administered nightly to CP (Cerebral Palsy) patients to more effectively reduce the muscle spasms that disrupt sleep, it was shown to improve sleep efficiency, decrease sleep fragmentation and improve the sleep cycle. This improvement in night-time sleep was translated into a potential improvement in next-day functioning (improvement in next-day measures of spasticity and movement).

It is hypothesized that a similar type of improvement in sleep with consequent positive impact on next day improvement in spasticity, cognition and function, may also be manifest in a similar patient population, children with traumatic brain injury.

  Eligibility

Ages Eligible for Study:   8 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males/Females 8-18 years of age with documented history of TBI
  • Documented Loss of Consciousness(LOC) for more than 24 H, or initial GCS (Glasgow Coma Score) lower than 8
  • Current Spasticity that interferes with task performance
  • Patient is able to cooperate and understand general explanations

Exclusion Criteria:

  • History of allergy to tizanidine or any inactive component (including lactose intolerance)
  • Use of other hypnotic medication within 3 days of baseline visit and during the study
  • Botox therapy within 6 weeks of baseline, or use of Baclofen pump during the trial
  • Use of CYP1A2 inhibitors (ex. ciprofloxacin or fluvoxamine) for the duration of the study
  • Female patients on oral contraceptives
  • Significant abnormalities in clinical screening laboratory parameters (ALT, AST, Bilirubin>2 x uln; Creatinine>2 mg/dl;WBC <2300/mm3, platelets<80,000/mm3)
  • Taking of other medications that may adversely interfere with the actions of the study medication or outcome variables within 2 weeks of 5 half-lives of the baseline visit
  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: NCT00287157

Locations
Israel
Alyn Hospital Pediatric and Adolescent Rehabilitation Center
Jerusalem, Israel, 01090
Sponsors and Collaborators
Teva GTC
Investigators
Principal Investigator: Ido Yatsiv, MD Hadassah Medical Center, Ein Kerem, Jerusalem
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00287157     History of Changes
Other Study ID Numbers: Protocol C2/5/TZ-TBI-01
Study First Received: February 2, 2006
Last Updated: January 20, 2009
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Teva GTC:
Traumatic Brain Injury
Actigraphy
Spasticity, Cognition and Functioning

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Tizanidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Muscle Relaxants, Central
Neuromuscular Agents
Parasympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014