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

• ClinicalTrials.gov Identifier: NCT00287157
• Recruitment Status: Completed
• First Posted: February 6, 2006
• Last Update Posted: January 21, 2009
• Sponsor: Teva GTC
• Information provided by: Teva GTC

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Traumatic Brain Injury	Drug: Sublingual Tizanidine HCl	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: December 2006
• Actual Study Completion Date: May 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Improvement in Spasticity, Cognition and Daily Function [ Time Frame: 4 weeks ]

Secondary Outcome Measures :

1. Improvement in nighttime actigraphy sleep parameters [ Time Frame: 4 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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

• ClinicalTrials.gov Identifier: NCT00287157
• Other Study ID Numbers: Protocol C2/5/TZ-TBI-01
• First Posted: February 6, 2006
• Last Update Posted: January 21, 2009
• Last Verified: September 2007

Keywords provided by Teva GTC:

Traumatic Brain Injury; Actigraphy; Spasticity, Cognition and Functioning

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Tizanidine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; 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