Clinical trial NCT01463033: Levetiracetam to Prevent Post-Traumatic Epilepsy
Official title: Pilot: Levetiracetam to Prevent Post-Traumatic Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Post-traumatic Epilepsy
Keywords: Post-Traumatic epilepsy
Traumatic brain injury
Epilepsy prevention
Levetiracetam
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
Collaborators: name: Medstar Health Research Institute
First posted: 2011-11-01
Enrollment: 126
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Head injury is the cause of approximately 5% of all epilepsy in the US. Past attempts at preventing epilepsy by treatment with older antiepileptic drugs have been unsuccessful. Levetiracetam is a novel AED with potent antiepileptogenic properties in animal models of epilepsy. It has a favorable side effect and pharmacokinetic profile. It is therefore a strong candidate for a clinical trial of epilepsy prevention following traumatic brain injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI. The investigators propose to initiate the evaluation of levetiracetam in prevention of post-traumatic epilepsy by determining the safety, tolerability, pharmacokinetics and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post-traumatic epilepsy. Further, the investigators will follow subjects for 2 years after injury in order to obtain pilot data about effect of levetiracetam on PTE. This pilot study is the first step in evaluation of levetiracetam in prevention of post-traumatic epilepsy.


Eligibility criteria: Inclusion Criteria:

* Acute head injury associated with one of the following:

Intracranial hemorrhage, including epidural, subdural and intracerebral hemorrhage or with cerebral contusion(s) of any size; Penetrating (foreign body) head injury; Skull fracture and dural tear; Seizure within 8 hours of head injury

* Onset of head injury within 8-hours of proposed treatment initiation.
* Glasgow Coma Scale 6-15.

Exclusion Criteria:

* Clinical contraindications:

  * Previous epilepsy or status epilepticus.
  * Any systemic illness or unstable medical condition that might pose additional risk, including: renal insufficiency, other unstable metabolic or endocrine disturbances, and active systemic cancer.
  * Psychosis within six months of enrollment as determined by history of hospitalization for psychosis or medications for psychosis.
  * Moderate to severe mental retardation (IQ\< 55 or\>2 school grade levels below the expected for age \[expected age = grade level +5\]).
* Clinical/Laboratory Indicators:

  * Serum creatinine \> 1.5 on the day of treatment initiation for adults.
  * Serum creatinine ≥1.5 for subjects ≥17 years old, ≥1.0 for subjects 13-17 years old and ≥0.7 for subjects 6-12 years old.
  * Pregnancy
  * Use of any CNS-active investigational drugs within 3 months of enrollment.
  * Use of Antiepileptic Drugs (AEDs) within two months of enrollment, for any indication.
  * Allergy/sensitivity to study drugs or their formulations:
  * Active drug or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements:
  * Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Primary outcomes:
measure: Post-Traumatic Epilepsy
timeFrame: 2 years
Secondary outcomes:
measure: Adverse Events
timeFrame: 30 day treatment period
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: MedStar Research Institute
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Pavel Klein, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pearl PL, McCarter R, McGavin CL, Yu Y, Sandoval F, Trzcinski S, Atabaki SM, Tsuchida T, van den Anker J, He J, Klein P. Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy. Epilepsia. 2013 Sep;54(9):e135-7. doi: 10.1111/epi.12326. Epub 2013 Jul 22.
citation: Klein P, Herr D, Pearl PL, Natale J, Levine Z, Nogay C, Sandoval F, Trzcinsky S, Atabaki SM, Tsuchida T, van den Anker J, Soldin SJ, He J, McCarter R. Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy. Epilepsy Behav. 2012 Aug;24(4):457-61. doi: 10.1016/j.yebeh.2012.05.011. Epub 2012 Jul 7.
citation: Klein P, Herr D, Pearl PL, Natale J, Levine Z, Nogay C, Sandoval F, Trzcinski S, Atabaki SM, Tsuchida T, van den Anker J, Soldin SJ, He J, McCarter R. Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Arch Neurol. 2012 Oct;69(10):1290-5. doi: 10.1001/archneurol.2012.445.