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Preventing Epilepsy After Traumatic Brain Injury With Topiramate (PEPTO)

Primary Purpose

Traumatic Brain Injury, Epilepsy

Status

Terminated

Phase

Early Phase 1

Locations

Study Type

Interventional

Intervention

topiramate

phenytoin

About this trial

This is an interventional prevention trial for Traumatic Brain Injury focused on measuring tbi, traumatic brain injury, epilepsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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
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 -

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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

topiramate for 3 months after loading dose of phenytoin

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

Outcomes

Primary Outcome Measures

Early and late seizures after traumatic brain injury

Adverse events

Secondary Outcome Measures

Functional recovery after traumatic brain injury

Full Information

NCT ID

NCT00598923

First Posted

January 11, 2008

Last Updated

June 26, 2017

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT00598923

Brief Title

Preventing Epilepsy After Traumatic Brain Injury With Topiramate

Acronym

PEPTO

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 Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Terminated

Why Stopped

End of funding and low enrollment

Study Start Date

November 2004 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

February 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury, Epilepsy

Keywords

tbi, traumatic brain injury, epilepsy

7. Study Design

Primary Purpose

Prevention

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

topiramate for 3 months after loading dose of phenytoin

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

topiramate

Other Intervention Name(s)

Topamax

Intervention Description

100 mg twice per day for 3 months

Intervention Type

Drug

Intervention Name(s)

topiramate

Other Intervention Name(s)

Topamax

Intervention Description

100 twice per day for 6 days after loading dose of phenytoin

Intervention Type

Drug

Intervention Name(s)

phenytoin

Other Intervention Name(s)

Dilantin

Intervention Description

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

Primary Outcome Measure Information:

Title

Early and late seizures after traumatic brain injury

Time Frame

2 years

Title

Adverse events

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Functional recovery after traumatic brain injury

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 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 -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc A Dichter, MD, PhD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

12. IPD Sharing Statement

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Preventing Epilepsy After Traumatic Brain Injury With Topiramate

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