Use of Biperiden for the Prevention of Post-traumatic Epilepsy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Biperiden as a Disease Modifying Agent After Traumatic Brain Injury: a Placebo Controlled, Randomized, Double Blind Study

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: Biperiden Lactate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biperiden Lactate<br>5mg IV(in the vein)every 6 hours for 10 days | Drug: Biperiden Lactate<br>* 5mg IV(in the vein)every 6 hours for 10 days<br>* Other names: cinetol;|
| Placebo Comparator: Placebo<br>5mg IV(in the vein)every 6 hours for 10 days | Drug: Placebo<br>* 5mg IV(in the vein)every 6 hours for 10 days<br>* Other names: saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome: Indidence of post-traumatic epilepsy | The incidence of seizures will be evaluated starting immediately after TBI and continuously during the hospitalization period and after hospital discharge during the two year follow up period. Patients and their relatives will be asked to maintain a diary of seizures, and thus record all seizures with detailed descriptions of each event. The recordings will be evaluated in each patient visit. Seizures incidence will be compared between placebo and biperiden-treated patients. | 24 months after TBI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of seizures | The frequency of seizures will be counted starting immediately after TBI and continuously during the hospitalization period and after hospital discharge during the two year follow up period. Frequency of seizure will be compared between placebo and biperiden-treated patients. | 24 months after TBI | 
| Mortality and adverse effects | The incidence of death and adverse effects will be counted starting immediately after TBI and continuously during the hospitalization period and after hospital discharge during the two year follow up period. Incidence of death and adverse effects will be compared between placebo and biperiden-treated patients. | 24 months after TBI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biperiden, Post-traumatic Epilepsy, Traumatic Brain Injury