NCT01463033

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2005

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2005

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2008

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2010

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

October 12, 2011

Completed
20 days until next milestone

First Posted

Study publicly available on registry

November 1, 2011

Completed
4 years until next milestone

Results Posted

Study results publicly available

November 2, 2015

Completed
Last Updated

January 13, 2016

Status Verified

December 1, 2015

Enrollment Period

3.2 years

First QC Date

October 12, 2011

Results QC Date

November 11, 2014

Last Update Submit

December 11, 2015

Conditions

EpilepsyPost-traumatic Epilepsy

Keywords

Post-Traumatic epilepsyTraumatic brain injuryEpilepsy preventionLevetiracetam

Outcome Measures

Primary Outcomes (1)

  • Post-Traumatic Epilepsy

    occurrence of PTE (Post-Traumatic Epilepsy)

    2 years

Secondary Outcomes (1)

  • Adverse Events

    30 day treatment period

Study Arms (2)

Levetiracetam

ACTIVE COMPARATOR

66 subjects with acute head injury with a high risk for developing post-traumatic epilepsy will receive levetiracetam 55 mg/kg/day in a b.i.d. schedule. Treatment will commence within 8 hours of the acute head injury and will last for 30 days. In addition, subjects will receive phenytoin for 1 week following head injury as standard clinical care.

Drug: Levetiracetam

No Intervention Control

NO INTERVENTION

60 subjects with acute head injury with a high risk for developing post-traumatic epilepsy enrolled 8-24 hours after injury will not receive levetiracetam. Subjects will receive phenytoin for 1 week following head injury as standard clinical care.

Interventions

LevetiracetamDRUG

55 mg/kg/day given in 2 divided doses 12 hours apart

Also known as: Keppra (brand name)
Levetiracetam

Eligibility Criteria

Age6 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MedStar Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (3)

  • 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.

    PMID: 23876024RESULT

  • 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.

    PMID: 22771222RESULT

  • 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.

    PMID: 22777131RESULT

MeSH Terms

Conditions

EpilepsyEpilepsy, Post-TraumaticBrain Injuries, Traumatic

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesBrain InjuriesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

AcetamidesAmidesOrganic ChemicalsAcetatesAcids, AcyclicCarboxylic AcidsPyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Dr. Pavel Klein, P.I.
Organization
Children's National Medical Center
kleinp@epilepsydc.com
301-704-4925

Study Officials

  • Pavel Klein, M.D.

    Children's National Research Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

October 12, 2011

First Posted

November 1, 2011

Study Start

April 1, 2005

Primary Completion

June 1, 2008

Study Completion

February 1, 2010

Last Updated

January 13, 2016

Results First Posted

November 2, 2015

Record last verified: 2015-12

Locations

US(2)