PEPTO: Preventing Epilepsy After Traumatic Brain Injury With Topiramate

Sponsor

University of Pennsylvania (Other)

Overall Status

Terminated

CT.gov ID

NCT00598923

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Epilepsy	Drug: topiramate Drug: topiramate Drug: phenytoin	Early Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Preventing Epilepsy After Traumatic Brain Injury: A Pilot, Single-center Randomized Trial of Topiramate to Prevent Seizures After Moderate to Severe TBI

Study Start Date :

Nov 1, 2004

Actual Primary Completion Date :

Feb 1, 2009

Actual Study Completion Date :

Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 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 Other Names: Topamax
Experimental: 2 topiramate for 3 months after loading dose of phenytoin	Drug: topiramate 100 mg twice per day for 3 months Other Names: Topamax
Placebo Comparator: 3 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 Other Names: Dilantin

Arm

Intervention/Treatment

Experimental: 1

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

Other Names:

Topamax

Experimental: 2

topiramate for 3 months after loading dose of phenytoin

Drug: topiramate

100 mg twice per day for 3 months

Other Names:

Topamax

Placebo Comparator: 3

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

Other Names:

Dilantin

Outcome Measures

Primary Outcome Measures

Early and late seizures after traumatic brain injury [2 years]
Adverse events [2 years]

Secondary Outcome Measures

Functional recovery after traumatic brain injury [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
All four findings: Glasgow Coma Score = 3, no pupillary reaction, age > 45 years, and severe coagulopathy OR
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 -