Clinical trial NCT01048138: Use of Biperiden for the Prevention of Post-traumatic Epilepsy
Official title: Use of Biperiden as a Disease Modifying Agent After Traumatic Brain Injury: a Placebo Controlled, Randomized, Double Blind Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Traumatic Brain Injury
Keywords: Biperiden
Post-traumatic Epilepsy
Traumatic Brain Injury
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
First posted: 2010-01-13
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is no AED or medication that has been demonstrated to affect the development of post-traumatic epilepsy. Biperiden is a cholinergic antagonist, acting in the muscarinic receptor, that is widely used as an anti Parkinson drug. The investigators data with animal models of epilepsy indicate that anti-muscarinic agents might affect the natural course of the disease in the case of post-traumatic epilepsy.

Detailed description: Treatment with biperiden should be initiated in the first 12 hours after trauma as means to avoid the epileptogenic process. The treatment will be repeated every 6 hours for 10 consecutive days. The efficacy of biperiden as an antiepileptogenic drug will be established by analyzing the development of PTE between the biperiden and placebo groups. Several patients' aspects (clinical, electroencephalography, brain imaging, genetic and behavioral data) will be monitored for two year follow-up to unravel the mechanisms by which biperiden exerts its actions on epileptogenesis. The investigators are already at the early stages of patient's recruitment using the available resources.

Eligibility criteria: Inclusion Criteria:

* between 18 and 75 year of age
* patients with a diagnosis of acute TBI admitted to an emergency unit within 12 hours of the accident, regardless of the accident
* brain CT scan with signs of acute intraparenchymatous contusion
* signed informed consent (possibly by a relative)

Exclusion Criteria:

* malignant neoplasia and other severe comorbidities
* neurodegenerative disorders
* previous cerebrovascular accident
* record of convulsive seizures or use of anti-epileptic medication
* pregnancy
* concomitant use of the other anticholinergic medications
* presence of any factor that may contraindicate the use of biperiden
* participation in other clinical trial
* alcohol intoxication will not lead to exclusion of the subject.

Primary outcomes:
measure: Clinical Outcome: Indidence of post-traumatic epilepsy
timeFrame: 24 months after TBI
Secondary outcomes:
measure: Frequency of seizures
timeFrame: 24 months after TBI
measure: Mortality and adverse effects
timeFrame: 24 months after TBI
Other outcomes:
measure: Electroencephalogram Analysis: Presence of Epileptiform Discharges
timeFrame: during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
measure: Cognitive Assessments - Wechsler Adult Intelligence Scale (WAIS) - III
timeFrame: 6, 12 and 24 months after hospital discharge
measure: Quality of Life assessments - European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), EQ-VAS
timeFrame: 24 month after TBI
measure: Blood sampling biomarkers - Expression of miRNAs
timeFrame: 10 days or 18 months after TBI
measure: Blood sampling biomarkers - Expression of the ApoEϵ4 allele
timeFrame: 10 days or 18 months after TBI
measure: Blood sampling biomarkers - Expression of inflammatory cytokines
timeFrame: 10 days after TBI
measure: Brain Activity Biomarkers - Presence of high frequency oscillations
timeFrame: during first 10 days after TBI and 1, 3, 6, 12, 18 and 24 months after TBI
measure: Brain Activity Biomarkers - Presence of cortical spreading depression
timeFrame: during first 10 days after TBI
Locations:
city: Sao Paulo
country: Brazil
facility: Federal University of São Paulo
Study officials:
affiliation: Federal University of São Paulo
name: Luiz Mello
role: PRINCIPAL_INVESTIGATOR
References: