Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy (FLEET)
Flumazenil for Benzodiazepine Reversal in Electroconvulsive Therapy (FLEET): A Randomized Controlled Trial
The goal of this study is to investigate whether administering flumazenil to reverse the effects of benzodiazepines and/or zopiclone during electroconvulsive therapy (ECT) can help reduce cognitive side effects without diminishing treatment effectiveness in hospitalized patients with depression.
The investigators hypothesize that blockade of the GABA receptor with flumazenil will reduce cognitive side effects through improved seizures and a reduced need for electrical charge escalation during the ECT series. Cognitive side effects will be measured by the total score on the Screening for Cognitive Impairment in Psychiatry (SCIP) (primary outcome) at follow-up after completion of the ECT series. Furthermore, it is expected that the flumazenil strategy will reduce pre-treatment anxiety and improve patient satisfaction (secondary outcomes). In addition, flumazenil strategy is hypothesized to have beneficial effects on subjective cognitive complaints, autobiographical memory, and executive functioning (secondary outcomes). Finally, the flumazenil strategy is expected to be associated with more favorable structural and functional changes in executive functioning and memory-related brain networks after completion of the ECT series, which may, in turn, be linked to better overall cognition and autobiographical memory (secondary outcome measures). For exploratory purposes, the study will also examine longitudinal changes in depressive symptoms and cognitive outcomes from baseline to follow-up (tertiary outcomes).
Investigators will compare two different pre-ECT benzodiazepine management strategies:
- Flumazenil strategy (experimental): continued benzodiazepine and/or zopiclone use up until the time of the ECT session, followed by administration of flumazenil immediately prior to ECT
- Benzodiazepine withholding strategy (treatment as usual):
discontinuation of benzodiazepines and/or zopiclone prior to the ECT in accordance with standard clinical practice
調査の概要
状態
詳細な説明
The study will include adult inpatients (≥18 years of age) diagnosed with a mood disorder (major depressive disorder or bipolar disorder), currently experiencing a depressive episode (ICD-10: F31.3-5, F32 or F33), who are deemed eligible for ECT by a treating psychiatrist who is not affiliated with the study. Based on a power analysis, 132 participants (66 per group) are required to achieve adequate statistical power. To account for an anticipated 10% dropout rate from baseline to follow-up, the investigators will recruit 145 participants. Recruitment will be carried out through psychiatric hospital wards within the Mental Health Services of the Capital Region of Denmark.
Participants will be randomized following an initial screening to confirm eligibility. Randomization will be conducted using the automated randomization module in the Research Electronic Data Capture (REDCap) system, based on a pre-generated randomization list with variable block sizes of two and four. Allocation will be stratified by age (< 60 or ≥ 60 years) and electrode placement (unilateral vs. bilateral). Randomization will occur no later than the day prior to the second ECT session of the treatment series. Primary outcome assessors are blinded to the group allocation.
Baseline assessments will be conducted the day before the first ECT session or, if not otherwise possible, the day before the second ECT session. Participants will complete a brief neuropsychological assessment comprising the Screen for Cognitive Impairment in Psychiatry (SCIP) and additional measures of executive functioning and autobiographical memory. Participants will also complete self-report questionnaires assessing subjective cognitive complaints. Depressive symptom severity will be rated using the Hamilton Depression Rating Scale (HDRS).
During the ECT treatment series, repeated assessments will be conducted for each session. Participants will provide self-reported ratings of pre-treatment anxiety shortly before the session, while clinicians will record measures of seizure architecture, and time to reorientation following the session.
Follow-up assessments will be conducted 3-7 days after completion of the ECT-series, which serves as the primary end point. At follow-up, the brief neuropsychological assessment, self-report questionnaires, and HDRS ratings will be repeated. Participants will also complete a short self-report questionnaire of their treatment satisfaction. Structural and functional magnetic resonance imaging (MRI) is conducted within the 3-7 days after completion of the ECT series, coinciding with the follow-up assessment.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Stella K. S. Lystlund, MSc in Psychology
- 電話番号：+ 45 21 35 40 55
- メール：stella.klara.soerensdottir.lystlund@regionh.dk
研究連絡先のバックアップ
- 名前：Yunus Kiros, MD
- 電話番号：+ 45 81 71 95 29
- メール：yunus.kiros.02@regionh.dk
研究場所
-
-
Capital Region
-
Frederiksberg、Capital Region、デンマーク、2000
- 募集
- Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion criteria:
- Current depressive episode (unipolar or bipolar), corresponding to ICD-10 codes F31.3-5, F32 or F33.
- Admitted at a study affiliated department in the Mental Health Services of the Capital Region of Denmark
- Referred to ECT by the regular psychiatrist and has given consent to ECT
- Currently receiving treatment with a benzodiazepine and/or zopiclone, at a minimum daily dose equivalent to 0.5 mg lorazepam.
Exclusion criteria:
- Involuntary treatment with ECT
- Known gross abnormalities in brain structure deemed likely to influence cognitive functioning
- Pregnancy or breast-feeding
- Inability to read or understand Danish
- Acute organic brain disease (e.g., delirium) influencing the ability to give informed consent
- Any pre-existing condition associated with an increased risk of prolonged or uncontrollable seizures, including but not limited to epilepsy or alcohol- or benzodiazepine withdrawal states
- Conditions associated with reduced metabolism of flumazenil (e.g., liver failure)
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：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Flumazenil for benzodiazepine reversal
Participants continue benzodiazepine and/or zopiclone treatment up until the ECT session, receiving flumazenil to reverse their effects
|
The intervention involves continuation of benzodiazepine and/or zopiclone treatment up to the time of ECT, followed by administration of flumazenil immediately prior to anesthesia to transiently reverse the effect of benzodiazepines and/or zopiclone.
Otherwise, ECT is administered according to standard clinical procedures.
|
|
アクティブコンパレータ：Treatment as usual (benzodiazepine hold)
Participants discontinue benzodiazepine and/or zopiclone treatment the day prior to the ECT session.
|
Standard ECT treatment performed in accordance with clinical practice, with benzodiazepines and/or zopiclone withheld after 5:00 p.m. on the day before each session
|
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 |
|---|---|---|
|
Screen for Cognitive Impairment in Psychiatry (SCIP)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
The primary outcome measure is the total score on the SCIP at follow-up (post-ECT).
The SCIP is a brief neuropsychological assessment tool designed to detect cognitive deficits in individuals with psychotic and affective disorders.
It comprises five subtests assessing key cognitive domains: verbal learning and memory (VLT-I and VLT-D), working memory (WMT), verbal fluency (VFT), and processing speed (PST).
The total score provides a broad indicator of overall cognitive functioning.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Hamilton Depression Rating Scale (HDRS)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
Clinician-administered depression assessment scale of 17 items.
Score range: 0-52.
Clinical response at follow-up (primary endpoint) is assessed using the HAM-D6 subscale, collectively comprising the core symptoms of depression with score range: 0-22.
Higher scores mean a worse outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
Self-report questionnaire assessing subjective cognitive complaints.
Score range: 0-48.
Higher scores mean a worse outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Squire Subjective Memory Questionnaire (SSMQ)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
Self-report questionnaire assessing subjective memory complaints.
Score range: -72 - +72.
Higher (more positive) scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Autobiographical Memory Test (AMT)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
Neuropsychological instrument used to assess the ability to retrieve autobiographical memories and their specificity.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Trail Making Test B (TMT-B)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
Neuropsychological test assessing executive function.
Scored by time to completion.
Higher scores mean a worse outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Verbal learning and memory (VLT-I)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
SCIP subtest assessing verbal learning and immediate recall.
Score range: 0-30.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Delayed verbal recall (VLT-D)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
SCIP subtest assessing delayed verbal recall.
Score range: 0-10.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Working memory test (WMT)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
SCIP subtest assessing working memory capacity.
Score: 0-24.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Verbal fluency test (VFT)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
SCIP subtest assessing verbal fluency.
No score range.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Processing speed test (PST)
時間枠：Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
SCIP subtest assessing processing speed.
Score range: 0-30.
Higher scores mean a better outcome.
|
Baseline (the day before the first or second session in the ECT series) and follow-up (3-7 days after completion of the ECT series)
|
|
Patient Satisfaction Survey (PSS)
時間枠：Follow-up (3-7 days after completion of the ECT series)
|
Self-report questionnaire assessing patient satisfaction following ECT treament.
A subset of items are used.
Higher scores mean a better outcome.
|
Follow-up (3-7 days after completion of the ECT series)
|
|
Visual Analogue Scale for Anxiety (VAS-A)
時間枠：Per ECT session
|
Visual analogue self-report scale assessing anxiety severity within the last 24 hours.
Score range: 0-100.
Higher scores mean a worse outcome.
|
Per ECT session
|
|
Time to reorientation
時間枠：Per ECT session
|
Clinician-administered structured interview measuring time to reorientation (in minutes) according to Sobin et al. (1995) and Stuiver et al. (2024).
Patients are screened every 5 minutes after EEG-offset for orientation in five domains: name, location, age, date of birth, and day of the week.
Reorientation is defined as the time in minutes from EEG-offset until the patient provides at least 4 out of 5 correct answers.
If the patient fails to reach reorientation within 60 minutes, a score of 70 minutes is registered.
Higher scores indicate a longer recovery period and a worse outcome.
|
Per ECT session
|
|
Seizure quality
時間枠：Per ECT session
|
Clinician-rated categorical EEG classification of seizure quality (A, A-T, T, O, S).
A-seizures represent the optimal therapeutic pattern.
|
Per ECT session
|
|
Seizure length (EEG)
時間枠：Per ECT session
|
EEG seizure duration (seconds) from the end of stimulation to the last unequivocal ictal discharge.
Continuous physiological measure.
|
Per ECT session
|
|
Stimulus dose
時間枠：Per ECT session
|
Stimulus dose recorded as the percentage of the device's maximum output (%) delivered during each treatment, as displayed on the ECT device readout.
Range: 0-200%.
|
Per ECT session
|
|
Prefrontal and medial temporal activation during autobiographical memory retrieval
時間枠：Follow-up (3-7 days after completion of the ECT series)
|
Functional magnetic resonance imaging (fMRI) measure of brain activity during an autobiographical memory test
|
Follow-up (3-7 days after completion of the ECT series)
|
|
Prefrontal, parietal and medial temporal activation during memory encoding
時間枠：Follow-up (3-7 days after completion of the ECT series)
|
Functional magnetic resonance imaging (fMRI) measure of brain activity during a memory encoding task
|
Follow-up (3-7 days after completion of the ECT series)
|
|
Prefrontal and parietal activation during spatial N-back
時間枠：Follow-up (3-7 days after completion of the ECT series)
|
Functional magnetic resonance imaging (fMRI) measure of brain activity during a working memory task
|
Follow-up (3-7 days after completion of the ECT series)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Anders Jørgensen, MD, Ph.D.、Mental Health Services of the Capital Region
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
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
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2025-522506-20-00
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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。