Preventing Epilepsy After Traumatic Brain Injury With Topiramate

NCT00598923 | Terminated Early Phase 1

• 1 other identifier: PR043514
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Traumatic Brain Injury; Epilepsy

Keywords

tbi; traumatic brain injury; epilepsy

Outcome Measures

Primary Outcomes (2)

• Early and late seizures after traumatic brain injury

  2 years

• Adverse events

  2 years

Secondary Outcomes (1)

• Functional recovery after traumatic brain injury

  2 years

Study Arms (3)

1

EXPERIMENTAL

Phenytoin 20mg/kg load, then Topiramate, 100 mg twice daily, starting at 24 hours post-TBI for 6 days.

Drug: topiramate

2

EXPERIMENTAL

topiramate for 3 months after loading dose of phenytoin

Drug: topiramate

3

PLACEBO COMPARATOR

Phenytoin 20 mg/kg as loading dose than 300 mg/day for total of 7 days

Drug: phenytoin

Interventions

topiramate DRUG

100 mg twice per day for 3 months

Also known as: Topamax

2

phenytoin DRUG

loading dose of 20 mg/kg and then 300 mg/day for total of 7 days

Also known as: Dilantin

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. -

You may not qualify if:

• 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 -

Sponsors & Collaborators

• University of Pennsylvania: lead

MeSH Terms

Conditions

Brain Injuries, Traumatic; Epilepsy

Interventions

Topiramate; Phenytoin

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Marc A Dichter, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2008
• First Posted: January 23, 2008
• Study Start: November 1, 2004
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: June 27, 2017

Record last verified: 2017-06