Use of Biperiden for the Prevention of Post-traumatic Epilepsy

June 17, 2021 updated by: Luiz Eugenio Mello, Federal University of São Paulo

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Treatment with biperiden will 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
132

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
      • Sao Paulo, Brazil
        • Recruiting
        • Federal University of São Paulo
        • Contact:
        • Principal Investigator:
          • Luiz EM Mello

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • between 18 and 75 year of age
  • patients with a diagnosis of severe TBI admitted to an emergency unit within 6 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
  • cerebrovascular accident in the previous 6 months
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Biperiden Lactate
5mg IV(in the vein)every 6 hours for 10 days
Drug: Biperiden Lactate
5mg IV(in the vein)every 6 hours for 10 days
Other Names:
  • akineton
  • cinetol
Placebo Comparator: Placebo
5mg IV(in the vein)every 6 hours for 10 days
Drug: Placebo
5mg IV(in the vein)every 6 hours for 10 days
Other Names:
  • saline solution

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Clinical Outcome: Seizure Frequency
Time Frame: during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
The number 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. 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 frequency will be compared between placebo and biperiden-treated patients.
during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
Electroencephalogram Analysis: Presence of Epileptiform Discharges
Time Frame: during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
Scalp EEG monitoring will be continuously registered during the first 10 days after TBI. After that, brain activity will be monitored weekly until hospital discharge. Chronically, EEG follow up monitoring will occur 1, 3, 6, 9, 12, 18 and 24 months after TBI. The presence of epileptiform abnormalities (rhythms, spikes, paroxysms, coherence, synchrony and power spectrum of different waveforms, e.g. Alpha, Beta, Theta) will be investigated. The occurrence of epileptiform discharges (and also ictal activity, and changes in the pattern of interictal discharges) will be compared between placebo and biperiden-treated patients.
during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cognitive Assessments - Wechsler Adult Intelligence Scale (WAIS) - IV
Time Frame: 1, 12 and 24 months after hospital discharge
Cognitive effects of the biperiden therapy will be assessed to demonstrate the efficacy and safety of this medicine in face of its possible cognitive implications. The instruments selected to assess those are tests of the Wechsler Adult Intelligence Scale (WAIS) - IV. The WAIS-IV returns scores on four separate indexes of adult intelligence, the Perceptual Reasoning Index, the Verbal Comprehension Index, the Working Memory Index and the Processing Speed Index. Scores will be calculated on each of the 4 indices and then combined to create a Full-Scale IQ. The WAIS-IV is normed so that 100 is the median score for the adult population (score ranges: 120-129= superior, 110-119= high average, 90-109=average, 80-89= low average, 71-80= borderline intellectual functioning, 50-70= moderate retardation, below 50= severe retardation. The battery of tests will be applied at specific time frames and results will be compared.
1, 12 and 24 months after hospital discharge
Quality of Life assessments - Quality of Life after Brain Injury (QOLIBRI)
Time Frame: 12 and 24 month after hospital discharge
The Portuguese version of the QOLIBRI (Quality of Life after Brain Injury) questioner will be used to assess health-related quality of life (HRQoL), 12 and 24 months after TBI. This is the first instrument specifically developed to assess quality of life of individuals after TBI. It consists of a questionnaire with 37 items covering six dimensions of HRQoL (cognition, self, daily life and autonomy, social relationships, emotion, physical problems). The responses on each scale are summed to give a total (range form 1 to 5), and then divided by the number of responses to give a scale mean. The QOLIBRI Total score is calculated by summing all the responses, and then dividing by the actual number of responses. The scale means are converted to the 0-100 scale by subtracting 1 from the mean and then multiplying by 25. This produces scale scores which have a lowest possible value of 0 (worst possible quality of life) and a maximum value of 100 (best possible quality of life).
12 and 24 month after hospital discharge
Neuroimaging techniques - Magnetic Resonance Imaging (MRI) and computed tomography (CT) scan
Time Frame: Measured as soon as possible after TBI, 10 days and 12 months after TBI
Exams including conventional MRI and/or CT scan will be obtained at service admission or as soon as possible following neurosurgeon criteria to confirm evidence of acute intraparenchymal hemorrhage and will be repeated as necessary during hospitalization. Additionally, MRI will be repeated at 10 days after TBI, and also at 1 and 12 months after hospital discharge. MRI lesions will be classified and evaluated regarding their size, location, number, volume and shape, among other factors (T2 flair, DWI, SWI and resting state). Neuroanatomic characteristics evidenced by MRI will be correlated with the incidence of seizures in the follow up assessments after TBI.
Measured as soon as possible after TBI, 10 days and 12 months after TBI
Blood sampling biomarkers - Expression of miRNAs
Time Frame: 10 days and 1 year after TBI
Alterations in expression of miRNAs will be assayed in blood samples during treatment with biperiden and again one year after trauma. Patterns of changes in the miRNA levels will be compared between the groups of patients that developed post-traumatic epilepsy or did not develop epilepsy.
10 days and 1 year after TBI
Blood sampling biomarkers - Expression of the ApoEϵ4 allele
Time Frame: 10 days after TBI
To investigate the expression of the ApoEϵ4 allele in TBI patients, and its correlation with post-traumatic epilepsy development and the biperiden treatment efficacy to prevent epilepsy, RFLP-PCR will be assayed in blood samples of TBI patients. The genotyping reactions will be performed blinded to clinical features. The presence of the ApoEϵ4 allele will be correlated with the incidence of seizures in the follow up assessments after TBI.
10 days after TBI
Blood sampling biomarkers - Expression of inflammatory cytokines
Time Frame: 10 days and 1 year after TBI
To verify whether cytokines are differently involved on PTE development, we will perform multi-analyte protein profile in blood plasma samples collected during treatment with biperiden and one year after TBI. Simultaneous measuring of different proteins in plasma will be performed. The concentration of each analyte will be normalized to the total protein concentration and presented as a proportion of specific proteins in picograms (pg) per microgram (μg) of total protein. Patterns of protein expression will be correlated with the incidence of seizures in the follow up assessments after TBI.
10 days and 1 year after TBI

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Brain Activity Biomarkers - Presence of high frequency oscillations
Time Frame: during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
Given the requirement of specific adjustments in the EEG recording apparatus (10 KHz sampling rate, high-pass filter above 80 Hz for ripples and 250 Hz for fast ripples), only a subset of patients will be included in this outcome. EEG will be continuously registered during the first 10 days after TBI, weekly until hospital discharge and at specified time frames after TBI. The presence of high frequency oscillations (ripples and fast ripples) will be investigated.
during first 10 days after TBI and 1, 3, 6, 9, 12, 18 and 24 months after TBI
Brain Activity Biomarkers - Presence of cortical spreading depression
Time Frame: during first 10 days after TBI
Given the requirement of specific adjustments in the EEG recording apparatus (e.g., direct current [DC] recording) to detect cortical spreading depression, a subset of patients will be EEG continuously registered during the first 10 days after trauma with other recording specifications. The presence of cortical spreading depression activity will be investigated.
during first 10 days after TBI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Federal University of São Paulo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Sao Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rafael Loduca, Federal University of São Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 12, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 13, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 18, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CEP0560/05

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings