Priming the Epileptic Brain: tVNS to Improve Efficacy of add-on AED in Patients With Focal Epilepsy (PREP)
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
調査の概要
詳細な説明
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.
研究の種類
入学 (予想される)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前:Angelique A Stuurman, Msc
- 電話番号:0031402279777
- メール:prep@tue.nl
研究連絡先のバックアップ
- 名前:Rob R Mestrom, Dr
- 電話番号:0031402279777
- メール:prep@tue.nl
研究場所
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Noord Brabant
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Heeze、Noord Brabant、オランダ、5590 AB
- 募集
- Stichting Kempenhaeghe
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コンタクト:
- Angelique Stuurman
- 電話番号:0031 0402279777
- メール:prep@tue.nl
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
アクティブコンパレータ:Brivaracetam + Transcutaneous vagal nerve stimulation
Start of Brivaracetam (treatment as usual), combined with tVNS in the first 3 months of treatment
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Cerbomed NEMOS
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介入なし:Brivaracetam
Start of Brivaracetam (treatment as usual)
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Epilepsy frequency
時間枠:6 months
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Seizure reduction (in % at 3 and 6 months in respect to baseline)
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6 months
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Epilepsy frequency
時間枠:6 months
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Seizure freedom rates (defined as the percentage of subjects with 100% reduction from baseline seizure frequency)
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6 months
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Seizure severity
時間枠:6 months
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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).
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6 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Brain networks
時間枠:3 months
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Detect changes in network properties by comparing fMRI (functional MRI) data at 3 months with baseline (independent component analysis)
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3 months
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協力者と研究者
捜査官
- 主任研究者:Marian M Majoie, Prof. Dr.、ACE Kempenhaeghe
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
TVNSの臨床試験
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Foundation for Prader-Willi ResearchRTI International募集
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Krankenhaus HetzelstiftJohannes Gutenberg University Mainz; Deutsche Stiftung für Herzforschung募集
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Fondazione Toscana Gabriele MonasterioAzienda Ospedaliera Città della Salute e della Scienza di Torinoまだ募集していません
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Istituti Clinici Scientifici Maugeri SpA募集
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University of California, Los AngelesUniversity of Oklahoma募集