Focal EpilepsyPREPNCT05180916
Priming the Epileptic Brain: tVNS to Improve Efficacy of add-on AED in Patients With Focal Epilepsy
A study testing TVNS in people with Focal Epilepsy, run by Eindhoven University of Technology at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Focal Epilepsy
- What is being tested?
- TVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2021to 1 Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- - 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)
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Stichting Kempenhaeghe
Heeze, North Brabant, 5590 AB
Angelique Stuurman, 0031 0402279777, prep@tue.nl
About this study
Official title: Priming the Epileptic Brain - Determining the Effect of Temporarily Addition of Transcutaneous Vagal Nerve Stimulation When Starting an add-on AED (in This Case Brivaracetam) in Patients With Refractory Focal Epilepsy
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.
Read the 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
- Being tested
- TVNS
- Keywords
- vagus nerve stimulation
- Medical subject headings
- Epilepsies, Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TVNSDevice
Cerbomed NEMOS
| Study group | Role | What they receive |
|---|---|---|
| Brivaracetam + Transcutaneous vagal nerve stimulation | Active comparator | Start of Brivaracetam (treatment as usual), combined with tVNS in the first 3 months of treatment Receives: Device: TVNS |
| Brivaracetam | No intervention | Start of Brivaracetam (treatment as usual) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epilepsy frequency
Seizure reduction (in % at 3 and 6 months in respect to baseline)
Measured: 6 months
Epilepsy frequency
Seizure freedom rates (defined as the percentage of subjects with 100% reduction from baseline seizure frequency)
Measured: 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).
Measured: 6 months
Secondary outcomes (1)
Brain networks
Detect changes in network properties by comparing fMRI (functional MRI) data at 3 months with baseline (independent component analysis)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2022
- Study start1 Aug 2021
- Primary completion1 Jul 2023 (estimated)
- Study completion1 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controlled trial
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eindhoven University of Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Trial Center Maastricht B.V.
- Responsible party
- Sponsor
- Investigators
- Marian M Majoie, Prof. Dr., Principal investigator, ACE Kempenhaeghe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05180916
- Sponsor's protocol ID
- PREP_001
- Acronym
- PREP
- Status last verified
- Dec 2021
- First submitted
- 2 Jul 2021
- Last updated
- 6 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Priming the Epileptic Brain - Determining the Effect of Temporarily Addition of Transcutaneous Vagal Nerve Stimulation When Starting an add-on AED (in This Case Brivaracetam) in Patients With Refractory Focal Epilepsy
- ClinicalTrials.gov ID
- NCT05180916
- Acronym / sponsor ID
- PREP / PREP_001
- Conditions
- Focal Epilepsy
- Keywords
- vagus nerve stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Eindhoven University of TechnologyUniversity, hospital or other
- Collaborators
- Clinical Trial Center Maastricht B.V.
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 1 Jul 2023 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 6 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized Controlled trial
| Arm | Type | Receives |
|---|---|---|
| Brivaracetam + Transcutaneous vagal nerve stimulation | Active comparator | Device: TVNSStart of Brivaracetam (treatment as usual), combined with tVNS in the first 3 months of treatment |
| Brivaracetam | No intervention | –Start of Brivaracetam (treatment as usual) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TVNSCerbomed NEMOS | Device | Brivaracetam + Transcutaneous vagal nerve stimulation |
Primary outcome
Epilepsy frequency
Time frame: 6 months
Seizure reduction (in % at 3 and 6 months in respect to baseline)
Epilepsy frequency
Time frame: 6 months
Seizure freedom rates (defined as the percentage of subjects with 100% reduction from baseline seizure frequency)
Seizure severity
Time frame: 6 months
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).
1 secondary outcome
Brain networks
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marian M Majoie, Prof. Dr. principal investigator
ACE Kempenhaeghe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TVNS in people with Focal Epilepsy, run by Eindhoven University of Technology at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Angelique A Stuurman, Msc (0031402279777, prep@tue.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epilepsy frequency (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2022.