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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00287157
Recruitment Status : Completed
First Posted : February 6, 2006
Last Update Posted : January 21, 2009
Information provided by:
Teva GTC

February 2, 2006
February 6, 2006
January 21, 2009
December 2006
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Improvement in Spasticity, Cognition and Daily Function [ Time Frame: 4 weeks ]
Improvement in Spasticity, Cognition and Daily Function
Complete list of historical versions of study NCT00287157 on Archive Site
Improvement in nighttime actigraphy sleep parameters [ Time Frame: 4 weeks ]
Improvement in nighttime actigraphy sleep parameters
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Pilot, Proof-of-Concept Study of Sublingual Tizanidine in Children With Chronic Traumatic Brain Injury (TBI)
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
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).

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.

Phase 1
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
Drug: Sublingual Tizanidine HCl
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 2007
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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
Sexes Eligible for Study: All
8 Years to 18 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
Protocol C2/5/TZ-TBI-01
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Teva GTC
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Principal Investigator: Ido Yatsiv, MD Hadassah Medical Center, Ein Kerem, Jerusalem
Teva GTC
September 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP