Biperiden for prevention of post-traumatic epilepsy: A protocol of a double-blinded placebo-controlled randomized clinical trial (BIPERIDEN trial)

PLoS One. 2022 Sep 9;17(9):e0273584. doi: 10.1371/journal.pone.0273584. eCollection 2022.

Abstract

Background: Traumatic brain injury (TBI) is one of the most important causes of acquired structural epilepsy, post-traumatic epilepsy (PTE), however, efficient preventative measures and treatment are still not available to patients. Preclinical studies indicated biperiden, an anticholinergic drug, as a potential drug to modify the epileptogenic process. The main objective of this clinical trial is to evaluate the efficacy of biperiden as an antiepileptogenic agent in patients that suffered TBI.

Methods: This prospective multicenter (n = 10) interventional study will include 312 adult patients admitted to emergency care units with a diagnosis of moderate or severe TBI. Following inclusion and exclusion criteria, patients will be randomized, using block randomization, to receive double-blind treatment with placebo or biperiden for 10 days. Follow-up will occur at specific time windows up to 2 years. Main outcomes are incidence of PTE after TBI and occurrence of severe adverse events. Other outcomes include exploratory investigation of factors that might have benefits for the treatment or might influence its results, such as genetic background, clinical progression, electroencephalographic abnormalities, health-related quality of life and neuropsychological status. Analyses will be conducted following the safety, intention-to-treat and efficacy concepts.

Discussion: We hypothesize that biperiden treatment will be effective to prevent or mitigate the development of post-traumatic epilepsy in TBI patients. Other health measures from this population also may benefit from treatment with biperiden.

Trial registration: ClinicalTrials.gov, NCT04945213. Registered on June 30, 2021.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biperiden* / therapeutic use
  • Double-Blind Method
  • Epilepsy, Post-Traumatic* / prevention & control
  • Humans
  • Multicenter Studies as Topic
  • Prospective Studies
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Biperiden

Associated data

  • ClinicalTrials.gov/NCT04945213

Grants and funding

The study is funded by Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS, Brazil) (NUP 25000.014325/2021-33). LEM has a grant from FAPESP (18/24561-5) and from CNPq (311619/2019-3). The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.