Traumatic Brain InjuryEarly Phase 1PEPTONCT00598923
Preventing Epilepsy After Traumatic Brain Injury With Topiramate
A Early Phase 1 study testing topiramate and phenytoin in people with Traumatic Brain Injury and Epilepsy, run by University of Pennsylvania.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury, Epilepsy
- What is being tested?
- topiramate and phenytoin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- Nov 2004to Feb 2009
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. -
Who cannot join
- 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
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- 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 -
About this study
Official title: Preventing Epilepsy After Traumatic Brain Injury: A Pilot, Single-center Randomized Trial of Topiramate to Prevent Seizures After Moderate to Severe TBI
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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Epilepsy
- Being tested
- topiramate, phenytoin
- Keywords
- tbi, traumatic brain injury, epilepsy
- Medical subject headings
- Brain Injuries, Traumatic, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topiramateDrug
Also called Topamax
100 mg twice per day for 3 months
topiramateDrug
Also called Topamax
100 twice per day for 6 days after loading dose of phenytoin
phenytoinDrug
Also called Dilantin
loading dose of 20 mg/kg and then 300 mg/day for total of 7 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Phenytoin 20mg/kg load, then Topiramate, 100 mg twice daily, starting at 24 hours post-TBI for 6 days. Receives: Drug: topiramate |
| 2 | Experimental | topiramate for 3 months after loading dose of phenytoin Receives: Drug: topiramate |
| 3 | Placebo comparator | Phenytoin 20 mg/kg as loading dose than 300 mg/day for total of 7 days Receives: Drug: phenytoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early and late seizures after traumatic brain injury
Measured: 2 years
Adverse events
Measured: 2 years
Secondary outcomes (1)
Functional recovery after traumatic brain injury
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2008 (estimated)
- Study startNov 2004
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: End of funding and low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc A Dichter, MD, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00598923
- Sponsor's protocol ID
- PR043514
- Acronym
- PEPTO
- Status last verified
- Jun 2017
- First submitted
- 11 Jan 2008
- Last updated
- 27 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Epilepsy After Traumatic Brain Injury: A Pilot, Single-center Randomized Trial of Topiramate to Prevent Seizures After Moderate to Severe TBI
- ClinicalTrials.gov ID
- NCT00598923
- Acronym / sponsor ID
- PEPTO / PR043514
- Conditions
- Traumatic Brain Injury, Epilepsy
- Keywords
- tbi, traumatic brain injury, epilepsy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of funding and low enrollment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Nov 2004
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 23 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: topiramatePhenytoin 20mg/kg load, then Topiramate, 100 mg twice daily, starting at 24 hours post-TBI for 6 days. |
| 2 | Experimental | Drug: topiramatetopiramate for 3 months after loading dose of phenytoin |
| 3 | Placebo comparator | Drug: phenytoinPhenytoin 20 mg/kg as loading dose than 300 mg/day for total of 7 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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. -
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| topiramateAlso: Topamax100 mg twice per day for 3 months | Drug | 2 |
| topiramateAlso: Topamax100 twice per day for 6 days after loading dose of phenytoin | Drug | 1 |
| phenytoinAlso: Dilantinloading dose of 20 mg/kg and then 300 mg/day for total of 7 days | Drug | 3 |
Primary outcome
Early and late seizures after traumatic brain injury
Time frame: 2 years
Adverse events
Time frame: 2 years
1 secondary outcome
Functional recovery after traumatic brain injury
Time frame: 2 years
Results and safety
The study was stopped early (reason given: End of funding and low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc A Dichter, MD, PhD principal investigator
University of Pennsylvania
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing topiramate and phenytoin in people with Traumatic Brain Injury and Epilepsy, run by University of Pennsylvania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: End of funding and low enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early and late seizures after traumatic brain injury (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2017.