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

Sponsored by:	Teva R&D Initiative
Information provided by:	Teva R&D Initiative
ClinicalTrials.gov Identifier:	NCT00287157

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 I

MedlinePlus related topics: Traumatic Brain Injury

Drug Information available for: Tizanidine Tizanidine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
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

Further study details as provided by Teva R&D Initiative:

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

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 R&D Initiative

Investigators

Principal Investigator:

Ido Yatsiv, MD

Hadassah Medical Center, Ein Kerem, Jerusalem

More Information

No publications provided

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

Keywords provided by Teva R&D Initiative:

Traumatic Brain Injury
Actigraphy
Spasticity, Cognition and Functioning

Study placed in the following topic categories:

Craniocerebral Trauma
Neurotransmitter Agents
Adrenergic alpha-Agonists
Adrenergic Agents
Wounds and Injuries
Central Nervous System Diseases
Disorders of Environmental Origin
Trauma, Nervous System
Brain Diseases

Adrenergic Agonists
Muscle Spasticity
Muscle Relaxants, Central
Peripheral Nervous System Agents
Analgesics
Tizanidine
Brain Injuries
Anticonvulsants

Additional relevant MeSH terms:

Craniocerebral Trauma
Parasympatholytics
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Disorders of Environmental Origin
Neuromuscular Agents
Brain Diseases
Adrenergic Agonists
Sensory System Agents
Therapeutic Uses
Muscle Relaxants, Central

Tizanidine
Analgesics
Brain Injuries
Adrenergic alpha-Agonists
Nervous System Diseases
Wounds and Injuries
Central Nervous System Diseases
Trauma, Nervous System
Pharmacologic Actions
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on May 07, 2009