Priming the Epileptic Brain: tVNS to Improve Efficacy of add-on AED in Patients With Focal Epilepsy

NCT ID: NCT05180916

Last Updated: 2022-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-01
• Study Completion Date: 2023-07-01

Brief Summary

The most prevalent neurological disorder with also immense burden of disease, epilepsy, is in over 30 percent of patients difficult to treat. The ideal treatment regime would give complete control of disease in an early stage, not only for patient well-being, but also to prevent the onset of persistent pathologic epileptic networks in the brain. The first step in treatment is the trial, and error, of multiple anti-epileptic drugs (AEDs), while invasive brain stimulation (BS) techniques with network modulating properties are saved as a last resort. The investigators hypothesize that pharmacotherapeutic treatment of epilepsy can be more successful after "priming" (preparing) the brain using BS as a short-term neuromodulation treatment. The limitation of testing this hypothesis is the invasive aspect of the most used classic vagal nerve stimulation (VNS) treatment for epilepsy, but the recent development of transcutaneous vagal nerve stimulation (tVNS) offered a possibility to combine chemical and electrical modulation in an earlier stage of disease, which is not tested before. The investigators want to determine the priming effect on the epileptic brain of tVNS, to make it more susceptible to add-on treatment with Brivaracetam (BRV), an AED. In addition, the investigators aim to visualize these changes in the brain because of priming, possibly altered network-organisation.

Detailed Description

Background of the study: The most prevalent neurological disorder with also immense burden of disease, epilepsy, is in over 30 percent of patients difficult to treat. The ideal treatment regime would give complete control of disease in an early stage, not only for patient well-being, but also to prevent the onset of persistent pathologic epileptic networks in the brain. The first step in treatment is the trial, and error, of multiple anti-epileptic drugs (AEDs), while invasive brain stimulation (BS) techniques with network modulating properties are saved as a last resort. The investigators hypothesize that pharmacotherapeutic treatment of epilepsy can be more successful after "priming" (preparing) the brain using BS as a short-term neuromodulation treatment. The limitation of testing this hypothesis is the invasive aspect of the most used classic vagal nerve stimulation (VNS) treatment for epilepsy, but the recent development of transcutaneous vagal nerve stimulation (tVNS) offered a possibility to combine chemical and electrical modulation in an earlier stage of disease, which is not tested before.

Objective of the study: Determine the priming effect on the epileptic brain of tVNS, to make it more susceptible to add-on treatment with Brivaracetam (BRV), an AED. In addition, the investigators aim to visualize these changes in the brain because of priming, possibly altered network-organisation.

Study design: Randomized Controlled Trial. Study population: Adults with a refractory (continuing of seizures despite 2 tried AEDs) focal epilepsy and therefore have an indication for start of Brivaracetam. Intervention (if applicable): One group receives transcutaneous vagal nerve stimulation (tVNS) 4 hours daily for the first 3 months of brivaracetam treatment. Primary study parameters/outcome of the study: Scoring on a composite index combining seizure reduction, improvement of cognition and quality of life. Secondary study parameters/outcome of the study (if applicable): Seizure reduction, seizure freedom rates, seizure severity, cognition, mood state, adverse events tVNS and brivaracetam, change in brain network properties.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable): Besides minor temporary side effects no risk is attributed to tVNS. Because of the study one extra visit is necessary, besides regular clinical follow-up. The 3 visits do require some more time than usual because of the questionnaires, MRI and short cognitive tests. The burden of the telephone calls is very limited, since it only consists of a few short questions. Patients with claustrophobia are excluded, but the requirement of lying still can be somewhat uncomfortable. The eye tracking device uses a camera in the video screen, with no burden at all.

Conditions

Focal Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brivaracetam + Transcutaneous vagal nerve stimulation

Start of Brivaracetam (treatment as usual), combined with tVNS in the first 3 months of treatment

Group Type: ACTIVE_COMPARATOR

TVNS

Intervention Type: DEVICE

Cerbomed NEMOS

Brivaracetam

Start of Brivaracetam (treatment as usual)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

TVNS

Cerbomed NEMOS

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Focal epilepsy which is refractory (at least 2 different AEDs tried) and therefore has an indication for start of brivaracetam
• Age ≥ 18 years.
• IQ > 70 defined as any form of secondary education

Exclusion Criteria

• - Inclusion not possible within 2 weeks after start of brivaracetam
• History of a progressive cerebral disorder (neurodegenerative diseases, tumours)
• History of psychogenic nonepileptic seizures (PNES)
• Inability to provide informed consent
• Any contra-indication for brivaracetam
• Current or recent use (exposed ≤ 90 days)
• Current or recent use (exposed ≤ 90 days) of levetiracetam
• Current treatment with neurostimulation
• Inability of handling the tVNS device personally
• Subjects that have a current diagnosis of cardiac arrhythmic disease
• Any contraindication for tVNS: pregnancy, active implants (such as cardiac pacemakers of cochlear implants) or cerebral shunts (e.g. ventriculo-peritoneal shunts with valve)
• Any contraindication for MRI: metallic foreign body, pacemaker, claustrophobia, pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trial Center Maastricht B.V.

OTHER

Sponsor Role: collaborator

Eindhoven University of Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marian M Majoie, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

ACE Kempenhaeghe

Locations

Stichting Kempenhaeghe

Heeze, North Brabant, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Angelique A Stuurman, Msc

Role: CONTACT

prep@tue.nl

0031402279777

Rob R Mestrom, Dr

Role: CONTACT

prep@tue.nl

0031402279777

Facility Contacts

Angelique Stuurman

Role: primary

prep@tue.nl

0031 0402279777

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

PREP_001

Identifier Type: -

Identifier Source: org_study_id