Levetiracetam to Prevent Post-Traumatic Epilepsy
Condition: Epilepsy; Post-traumatic Epilepsy
MeSH terms: Epilepsy; Epilepsy, Post-Traumatic
Intervention: Levetiracetam
Intervention description: 55 mg/kg/day given in 2 divided doses 12 hours apart
Intervention MeSH terms: Levetiracetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 126.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: Post-Traumatic epilepsy; Traumatic brain injury; Epilepsy prevention; Levetiracetam

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.