Working… Menu

Preventing Epilepsy After Traumatic Brain Injury With Topiramate (PEPTO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00598923
Recruitment Status : Terminated (End of funding and low enrollment)
First Posted : January 23, 2008
Last Update Posted : June 27, 2017
Information provided by (Responsible Party):
University of Pennsylvania

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: 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : November 2004
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

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 Name: Topamax

Experimental: 2
topiramate for 3 months after loading dose of phenytoin
Drug: topiramate
100 mg twice per day for 3 months
Other Name: 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 Name: Dilantin

Primary Outcome Measures :
  1. Early and late seizures after traumatic brain injury [ Time Frame: 2 years ]
  2. Adverse events [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Functional recovery after traumatic brain injury [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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
  2. Time since TBI less than 24 hours
  3. Age greater than or equal to 18 years
  4. Subject capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject's behalf. -

Exclusion Criteria:

  1. 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
  2. Administration of an antiepileptic drug before enrollment
  3. History of allergy to topiramate or phenytoin
  4. Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test (urine pregnancy test or serum beta-HCG) before randomization
  5. Compromised renal function with serum creatinine > 2
  6. Severe concurrent illness with life expectancy <6 months
  7. Treatment with another investigational agent for TBI
  8. Unable to take medications orally and contraindication to placement of nasogastric tube.
  9. 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
  10. Patients with a history of kidney stones or glaucoma.
  11. Inability to maintain adequate fluid intake while taking topiramate.
  12. Patients whose TBI is a result of self inflicted injury
  13. Patient's who are currently using illicit drugs -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00598923

Sponsors and Collaborators
University of Pennsylvania
Layout table for investigator information
Principal Investigator: Marc A Dichter, MD, PhD University of Pennsylvania
Layout table for additonal information
Responsible Party: University of Pennsylvania Identifier: NCT00598923    
Other Study ID Numbers: PR043514
First Posted: January 23, 2008    Key Record Dates
Last Update Posted: June 27, 2017
Last Verified: June 2017
Keywords provided by University of Pennsylvania:
traumatic brain injury
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Hypoglycemic Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers