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

NCT05180916 | Unknown

• 1 other identifier: PREP_001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Focal Epilepsy

Keywords

vagus nerve stimulation

Outcome Measures

Primary Outcomes (3)

• Epilepsy frequency

  Seizure reduction (in % at 3 and 6 months in respect to baseline)

  6 months

• Epilepsy frequency

  Seizure freedom rates (defined as the percentage of subjects with 100% reduction from baseline seizure frequency)

  6 months

• Seizure severity

  Assessed by the National Hospital Seizure Severity Scale - NHS3, comparing scores at 3 and 6 months to baseline). Score range 1-27 (higher score = more severe).

  6 months

Secondary Outcomes (1)

• Brain networks

  3 months

Study Arms (2)

Brivaracetam + Transcutaneous vagal nerve stimulation

ACTIVE COMPARATOR

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

Device: TVNS

Brivaracetam

NO INTERVENTION

Start of Brivaracetam (treatment as usual)

Interventions

TVNS DEVICE

Cerbomed NEMOS

Brivaracetam + Transcutaneous vagal nerve stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eindhoven University of Technology: lead
• Clinical Trial Center Maastricht B.V.: collaborator

Study Sites (1)

Stichting Kempenhaeghe

Heeze, North Brabant, 5590 AB, Netherlands

RECRUITING

MeSH Terms

Conditions

Epilepsies, Partial

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Marian M Majoie, Prof. Dr.

  ACE Kempenhaeghe

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angelique A Stuurman, Msc

CONTACT

0031402279777; prep@tue.nl

Rob R Mestrom, Dr

CONTACT

0031402279777; prep@tue.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled trial

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: January 6, 2022
• Study Start: August 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: January 6, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)