Preventing Epilepsy After Traumatic Brain Injury With Topiramate - Full Text View

Sponsored by:	University of Pennsylvania
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00598923

Purpose

Our hypothesis is that topiramate will reduce acute seizures after traumatic brain injury and will help prevent the development of epilepsy after traumatic brain injury.

Condition	Intervention	Phase
Traumatic Brain Injury Epilepsy	Drug: topiramate Drug: phenytoin	Phase II

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures Traumatic Brain Injury

Drug Information available for: Topiramate Phenytoin Phenytoin sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment
Official Title:	Preventing Epilepsy After Traumatic Brain Injury: A Pilot, Single-Center Randomized Trial of Topiramate to Prevent Seizures After Moderate to Severe TBI

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

Early and late seizures after traumatic brain injury [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Functional recovery after traumatic brain injury [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	November 2004
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Phenytoin 20mg/kg load, then Topiramate, 100 mg twice daily, starting at 24 hours post-TBI for 6 days.	Drug: topiramate 100 twice per day for 6 days after loading dose of phenytoin
2: Experimental topiramate for 3 months after loading dose of phenytoin	Drug: topiramate 100 mg twice per day for 3 months
3: Placebo Comparator Phenytoin 20 mg/kg as loading dose than 300 mg/day for total of 7 days	Drug: phenytoin loading dose of 20 mg/kg and then 300 mg/day for total of 7 days

Detailed Description:

Traumatic brain injury (TBI) causes epilepsy in up to 30% of civilian and 50% of military head injuries, exacerbating chronic neurological disability. There is currently no method for preventing epilepsy after TBI. We hypothesize that the new antiepileptic drug, topiramate (TPM), will (1) reduce acute seizures and prevent the development of epilepsy following TBI and (2) improve neurological recovery. We propose to perform a pilot clinical trial to develop the necessary infrastructure for larger scale randomized clinical trials to test TPM, and, possibly, other new antiepileptic drugs with neuroprotective properties, for their ability to prevent epilepsy after TBI. Subjects with TBI will be randomized within 24 hours to one of three groups: 1) TPM for one week, 2) TPM for three months, or 3) phenytoin for one week. Subjects will be followed for two years for the development of seizures and for neurological outcome. Serial EEGs and MRIs will be performed to explore potential mechanisms for the development of epilepsy after TBI. These new tools for the clinical study of epilepsy prevention, and neuroprotection in general, will be developed that can be applied to a wide variety of studies and which will facilitate future research in this critical area.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Moderate to severe traumatic brain injury, defined as one or more of the following: penetrating head wound seizure within the first hour after injury intracerebral hematoma or cortical contusion subdural or epidural hematoma Glasgow Coma Score <= 12 or motor score 1-5 (if intubated). Patients who have been pharmacologically paralyzed will be evaluated after the paralytic has worn off or been pharmacologically reversed depressed skull fracture requirement for emergent neurosurgical procedure
Time since TBI less than 24 hours
Age greater than or equal to 18 years
Subject capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject's behalf. -

Exclusion Criteria:

Known prior history of epilepsy or unprovoked seizures. Patients with a history of acute symptomatic seizures (e.g. febrile seizure, alcohol withdrawal seizure) will not be excluded
Administration of an antiepileptic drug before enrollment
History of allergy to topiramate or phenytoin
Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test (urine pregnancy test or serum beta-HCG) before randomization
Compromised renal function with serum creatinine > 2
Severe concurrent illness with life expectancy <6 months
Treatment with another investigational agent for TBI
Unable to take medications orally and contraindication to placement of nasogastric tube.
Irreversibly fatal TBI
1. All four findings: Glasgow Coma Score = 3, no pupillary reaction, age > 45 years, and severe coagulopathy OR
2. Severe brainstem lesion on neuroimaging studies
Patients with a history of kidney stones or glaucoma.
Inability to maintain adequate fluid intake while taking topiramate.
Patients whose TBI is a result of self inflicted injury
Patient's who are currently using illicit drugs -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00598923

Contacts

Contact: Kelly S Maxwell

215 614 0520

kelly.maxwell@uphs.upenn.edu

Locations

United States, Pennsylvania
Hospital of the University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Marc A Dichter, MD, PhD
Sub-Investigator: Susan T Herman, MD

Sponsors and Collaborators

University of Pennsylvania

Investigators

Principal Investigator:

Marc A Dichter, MD, PhD

University of Pennsylvania

More Information

Responsible Party:	University of Pennsylvania ( Dr. Marc A. Dichter )
Study ID Numbers:	PR043514
Study First Received:	January 11, 2008
Last Updated:	January 22, 2008
ClinicalTrials.gov Identifier:	NCT00598923
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

tbi
traumatic brain injury
epilepsy

Study placed in the following topic categories:

Craniocerebral Trauma
Phenytoin
Epilepsy
Seizures
Wounds and Injuries
Topiramate

Disorders of Environmental Origin
Central Nervous System Diseases
Trauma, Nervous System
Brain Diseases
Brain Injuries

Additional relevant MeSH terms:

Anti-Obesity Agents
Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases
Protective Agents

Neuroprotective Agents
Central Nervous System Agents
Pharmacologic Actions
Anticonvulsants

ClinicalTrials.gov processed this record on January 14, 2009