Biperiden Trial for Epilepsy Prevention

NCT ID: NCT04945213

Last Updated: 2024-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

312 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-10

Study Completion Date

2026-12-20

Brief Summary

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One of the most important neurological consequences following Traumatic Brain Injury (TBI) is the development of post traumatic epilepsy (PTE). Nevertheless, there is still no effective therapeutic intervention to reduce the occurrence of PTE. In previous studies with animals models of epilepsy, the biperiden decreased the incidence and intensity of spontaneous epileptic seizures besides delaying their appearance. The aim of this study is the evaluation of biperiden as antiepileptogenic drug to prevent PTE and also the determination of side effects, evaluating its cost-effectiveness in patients with moderate and severe TBI.

Detailed Description

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One of the most important neurological consequences following Traumatic Brain Injury (TBI) is the development of post traumatic epilepsy (PTE), which accounts for 5% of all epilepsy etiologies in the general population. This makes TBI one of the most important causes of secondary epilepsy, overcoming other causes such as infections, drug abuse or familiar history of epilepsy. The occurrence of spontaneous epileptic seizures after TBI, mostly starting in the first 2 years after moderate or severe TBI, might be as high as 86%, specially in those with a single acute symptomatic seizure, with remission rates of 25-40%. The causative relationship between TBI and epilepsy, as well as other types of epilepsy in general, are still not completely understood and PTE is not yet preventable.

The therapeutic approach indicated for TBI may involve medications, surgical procedures or both, with no effective therapeutic intervention to reduce its occurrence. Several experimental studies in animal models have shown that drugs, which modify processes of neuronal plasticity, have the potential to modify the natural course of PTE. Among these, biperiden (anti-cholinergic indicated for Parkinson's disease) has shown reduction in the incidence and intensity of spontaneous epileptic seizures and also delayed their occurence in animal epilepsy model. Thus Biperiden would be an excellent candidate for an antiepileptogenic agent. It is intended here to test its effectiveness and safety in adult patients, victims of moderate and severe TBI. Patients will be randomized to receive 5 mg of Biperiden iv, diluted in 100 ml of 0.9% saline (treatment group) or 1 mL of sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 mL of 0,9% saline (placebo group), every 6 hours for 10 days after TBI. Prospectively, patients will be followed up for two years, on periodic visits to assess the development of epileptic seizures. Other factors that might have benefits with the treatment, such as epileptiform abnormalities, genetic markers and neuropsychological aspects, will also be evaluated. The results could be important for a better comprehension of basic mechanisms of epilepsy development. Side effects of Biperiden use, at high doses during a short period of time, will be measured. If Biperiden is efficient and safe, it will certainly be a low-cost option for Brazilian public health system (SUS).

Conditions

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Brain Injury Traumatic Moderate Brain Injury Traumatic Severe Post Traumatic Epilepsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Biperiden

Drug: Biperiden 5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV

Group Type EXPERIMENTAL

Biperiden

Intervention Type DRUG

5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV

Placebo

Placebo

1 mL of sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 mL of 0,9% saline - every 6 hours for 10 consecutive days - IV

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

1ml sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 ml 0.9% saline - every 6 hours for 10 consecutive days - IV

Interventions

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Biperiden

5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV

Intervention Type DRUG

Placebo

1ml sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 ml 0.9% saline - every 6 hours for 10 consecutive days - IV

Intervention Type OTHER

Other Intervention Names

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Akineton Sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections)

Eligibility Criteria

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Inclusion Criteria

* Given informed consent
* 18 - 75 years of age
* GCS between 6 and 12 at hospital admission. GCS between 3 and 5 at hospital admission can be enrolled if patient was sedated at the accident scene with previous GCS between 6 and 15.
* Moderate or severe acute traumatic brain injury
* All genders
* Brain CT scan with signs of of acute intraparenchymal hemorrhage and/or contusion
* Able to receive the first dose of treatment or placebo within 18 hours of brain injury,

Exclusion Criteria

* Previous use of biperiden
* History of epilepsy (confirmed by patient chart)
* History of seizures or use of antiepileptic medication
* Pregnancy
* Participation in another clinical trial at the time of randomization
* History of neoplasia, neurodegenerative diseases; history of stroke, cognitive impairment, benign prostatic hyperplasia, atrioventricular block or any other cardiac arrhythmia, or glaucoma megacolon or mechanical obstruction
* Homeless patient
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PROADI-SUS

UNKNOWN

Sponsor Role collaborator

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role collaborator

University of Sao Paulo

OTHER

Sponsor Role collaborator

Santa Casa de Campo Grande

OTHER

Sponsor Role collaborator

Hospital Sao Rafael

OTHER

Sponsor Role collaborator

Santa Casa de Misericórdia de Sobral

UNKNOWN

Sponsor Role collaborator

Hospital de Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

UNKNOWN

Sponsor Role collaborator

Hospital São Paulo, Universidade Federal de São Paulo

UNKNOWN

Sponsor Role collaborator

Instituto Doutor José Frota

UNKNOWN

Sponsor Role collaborator

Hospital São Vicente de Paulo

UNKNOWN

Sponsor Role collaborator

Hospital Sirio-Libanes

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Luiz E Mello, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Sirio-Libanês

Eliana Garzon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Sirio-Libanês

Locations

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Instituto Doutor José Frota

Fortaleza, Ceará, Brazil

Site Status NOT_YET_RECRUITING

Santa Casa de Misericórdia de Sobral

Sobral, Ceará, Brazil

Site Status RECRUITING

Hospital Estadual Urgencia e Emergencia -HEUE

Vitória, Espírito Santo, Brazil

Site Status NOT_YET_RECRUITING

Hospital São Rafael

Salvador, Estado de Bahia, Brazil

Site Status RECRUITING

Associação Beneficente Santa Casa de Campo Grande

Campo Grande, Mato Grosso do Sul, Brazil

Site Status RECRUITING

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Site Status ACTIVE_NOT_RECRUITING

Hospital das Clínicas da Faculdade de Medicina da Universidade de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Site Status RECRUITING

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Hospital Sirio-Libanes

São Paulo, , Brazil

Site Status RECRUITING

Hospital São Paulo, Universidade Federal de São Paulo

São Paulo, , Brazil

Site Status NOT_YET_RECRUITING

Countries

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Brazil

Central Contacts

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Eliana Garzon, MD, PhD

Role: CONTACT

+55 (11) 98206-2308

Maira L Foresti, PhD

Role: CONTACT

+ 55(11) 958673803

Facility Contacts

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Carlos V Melo

Role: primary

Keven F Ponte, MD

Role: primary

Eva Cristino, MsC

Role: backup

Rodrigo C Ramos

Role: primary

Aparecida Taliule

Role: backup

Humberto Castro

Role: primary

Suane MS Mendonca

Role: backup

Eurico Feltrin, MD

Role: primary

André Afif

Role: backup

Guilherme GP Gondim, MD, PhD

Role: primary

RODRIGO B CERANTOLA

Role: backup

Almir F Andrade, MD, PhD

Role: primary

Saul Almeida, MD

Role: backup

Eliana Garzon, PhD

Role: primary

+55 (11) 982062308

Carla CG Pinheiro

Role: backup

+55 (11) 3394-4177

Luiz E Mello

Role: primary

References

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Antoniuk SA. [Non-epileptic disorders in infancy and adolescence]. Medicina (B Aires). 2013;73 Suppl 1:71-6. Spanish.

Reference Type BACKGROUND
PMID: 24072054 (View on PubMed)

Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998 Jan 1;338(1):20-4. doi: 10.1056/NEJM199801013380104.

Reference Type BACKGROUND
PMID: 9414327 (View on PubMed)

Aronstam, RS & Patil, P. Muscarinic Receptors: Autonomic Neurons, Encyclopedia of Neuroscience, Academic Press,2009; 1141-1149, ISBN 9780080450469, https://doi.org/10.1016/B978-008045046-9.00692-6.

Reference Type BACKGROUND

Anvisa. MANUAL PARA NOTIFICAÇÃO DE EVENTOS ADVERSOS E MONITORAMENTO DE SEGURANÇA EM ENSAIOS CLÍNICOS - 1a. edição. 2016. Disponível em: http://portal.anvisa.gov.br/documents/33836/2492465/Manual+para+Notifica%C3%A7%C3%A3o+de+Eventos+Adversos+e+Monitoramento+de+Seguran%C3%A7a+em+Ensaios+Cl%C3%ADnicos+-+1%C2%AA+Edi%C3%A7%C3%A3o/04a68574-8aac-43c9-b0b2-7b7cd80831c4. Acessado em 5 de novembro de 2019.

Reference Type BACKGROUND

Brady RD, Casillas-Espinosa PM, Agoston DV, Bertram EH, Kamnaksh A, Semple BD, Shultz SR. Modelling traumatic brain injury and posttraumatic epilepsy in rodents. Neurobiol Dis. 2019 Mar;123:8-19. doi: 10.1016/j.nbd.2018.08.007. Epub 2018 Aug 16.

Reference Type BACKGROUND
PMID: 30121231 (View on PubMed)

Bittencourt S, Ferrazoli E, Valente MF, Romariz S, Janisset NRLL, Macedo CE, Antonio BB, Barros V, Mundim M, Porcionatto M, Aarao MC, Miranda MF, Rodrigues AM, de Almeida AG, Longo BM, Mello LE. Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy. Epilepsy Res. 2017 Dec;138:88-97. doi: 10.1016/j.eplepsyres.2017.10.019. Epub 2017 Oct 29.

Reference Type BACKGROUND
PMID: 29096134 (View on PubMed)

D'Ambrosio R, Perucca E. Epilepsy after head injury. Curr Opin Neurol. 2004 Dec;17(6):731-5. doi: 10.1097/00019052-200412000-00014.

Reference Type BACKGROUND
PMID: 15542983 (View on PubMed)

da Silva AM, Vaz AR, Ribeiro I, Melo AR, Nune B, Correia M. Controversies in posttraumatic epilepsy. Acta Neurochir Suppl (Wien). 1990;50:48-51. doi: 10.1007/978-3-7091-9104-0_9.

Reference Type BACKGROUND
PMID: 2129092 (View on PubMed)

de Almeida CE, de Sousa Filho JL, Dourado JC, Gontijo PA, Dellaretti MA, Costa BS. Traumatic Brain Injury Epidemiology in Brazil. World Neurosurg. 2016 Mar;87:540-7. doi: 10.1016/j.wneu.2015.10.020. Epub 2015 Oct 17.

Reference Type BACKGROUND
PMID: 26485419 (View on PubMed)

DeVito NJ, Goldacre B. Catalogue of bias: publication bias. BMJ Evid Based Med. 2019 Apr;24(2):53-54. doi: 10.1136/bmjebm-2018-111107. Epub 2018 Dec 6. No abstract available.

Reference Type BACKGROUND
PMID: 30523135 (View on PubMed)

Englander J, Bushnik T, Duong TT, Cifu DX, Zafonte R, Wright J, Hughes R, Bergman W. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil. 2003 Mar;84(3):365-73. doi: 10.1053/apmr.2003.50022.

Reference Type BACKGROUND
PMID: 12638104 (View on PubMed)

Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Value Health. 2013 Mar-Apr;16(2):e1-5. doi: 10.1016/j.jval.2013.02.010.

Reference Type BACKGROUND
PMID: 23538200 (View on PubMed)

Benassi SK, Alves JGSM, Guidoreni CG, Massant CG, Queiroz CM, Garrido-Sanabria E, Loduca RDS, Susemihl MA, Paiva WS, de Andrade AF, Teixeira MJ, Andrade JQ, Garzon E, Foresti ML, Mello LE. Two decades of research towards a potential first anti-epileptic drug. Seizure. 2021 Aug;90:99-109. doi: 10.1016/j.seizure.2021.02.031. Epub 2021 Mar 3.

Reference Type BACKGROUND
PMID: 33714677 (View on PubMed)

Hauser WA, Annegers JF, Kurland LT. Prevalence of epilepsy in Rochester, Minnesota: 1940-1980. Epilepsia. 1991 Jul-Aug;32(4):429-45. doi: 10.1111/j.1528-1157.1991.tb04675.x.

Reference Type BACKGROUND
PMID: 1868801 (View on PubMed)

Foresti ML, Garzon E, Pinheiro CCG, Pacheco RL, Riera R, Mello LE. 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.

Reference Type DERIVED
PMID: 36084082 (View on PubMed)

Other Identifiers

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39005920810015461

Identifier Type: OTHER

Identifier Source: secondary_id

AVAP-NG 1983

Identifier Type: -

Identifier Source: org_study_id

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