Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- The effect of rivastigmine on scores of the verbal fluency test.
研究概览
简要总结
The goal of this clinical trial is to test the beneficial effects of rivastigmine administration, and predict the treatment outcome with electroencephalography (EEG), in patients with severe depression treated with electroconvulsive therapy (ECT). The study has two main objectives:
- to study whether rivastigmine would ameliorate the side-effect profile of ECT
- to develop an outcome prediction model based on resting state EEG for both the response to treatment as well as its side effect
Participants will be assessed by:
- Cognitive tests
- Questionnaires of clinical symptoms
- Questionnaires of depressive symptoms
- Bloodsample
- Resting state and task-based EEG
Researchers will compare patients with a depressive disorder treated with ECT receiving rivastigmine to placebo patches to see if rivastigmine reduces cognitive side effects.
详细描述
Electroconvulsive therapy (ECT) is the most potent psychiatric treatment, with an effect size of 1.5 for severe and refractory unipolar and bipolar depression. ECT convincingly outperforms pharmacotherapy such as tricyclic antidepressants and monoamine oxidase inhibitors and any form of psychotherapy. Despite its outstanding performance in reducing depressive symptoms up to the point of full remission, it is used only marginally. One reason for its infrequent use may be that the response to ECT is largely unpredictable, while cognitive side-effects occur frequently.
In a previous study, the researchers found that multiple cognitive tests showed a significant decline immediately post-ECT, which resolved within 6 months after the last ECT session without further treatment. Even though cognitive side-effects are mostly short-lasting, both patients and doctors see this as a great drawback of ECT. If these disturbing side-effects could be prevented, more patients and psychiatrists would choose ECT as a treatment option. This would lead to a more effective treatment and hence shorter duration of chronic severe depression and improvement in quality of life, while costs for health care and loss of productivity would decrease. A potential way of ameliorating side effects, could be to add a cholinesterase inhibitor to ECT treatment. Rodent studies show that the loss of cholinergic fibers specifically correlated to the cognitive side effects of rodents after electroconvulsive stimulation (ECS). The researchers selected rivastigmine (a cholinesterase inhibitor) as a potential candidate in counteracting cognitive side effects induced by cholinergic fiber loss due to ECT. Rivastigmine patches are very well tolerated and widely used for Alzheimer's and Parkinson's dementia.
Tailoring treatment to patients that are likely to respond while cognitive side-effects are unlikely to occur, would be another important improvement for depressed patients. Currently, ECT outcome is unpredictable. Factors that favor response include older age, psychotic depression, shorter duration of the depressive episode, and smaller volumes of the dentate gyrus (a part of the hippocampus). However, these predictors do not provide enough accuracy to make individual response profiles. Accurately classifying specifically non-responders will prevent application of ineffective treatment with potential iatrogenic damage, while more accurately predicted response will increase the applicability of ECT as treatment option. A potentially powerful way that is easy to implement in the clinic is prediction of ECT response using resting state EEG characteristics in addition to clinical information.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age over 18 years
- •Clinical indication for ECT (as indicated by the treating physician/psychiatrist)
- •Uni- or bipolar depression (as assessed by the treating psychiatrist)
- •Fluent in Dutch
排除标准
- •Currently receiving, or having received ECT 6 months prior to the start of the treatment/study.
- •Currently using rivastigmine, galantamine, donepezil (all cholinesterase inhibitors for mild to moderate Alzheimer's Disease).
- •Pregnancy and/or lactation/breast feeding
- •Suspicion of neurodegenerative disorders (as diagnosed earlier)
- •Contraindications for ECT (recent myocardial infarction, recent cerebrovascular accident, recent intracranial surgery, pheochromocytoma and instable angina pectoris)
- •Contraindications for rivastigmine (bradycardia or atrioventricular (AV) conduction disorders (first degree AV-block excluded)
- •Patients who have had an allergic reaction to rivastigmine
- •Cognitive disorder not explained by the depressive episode
研究组 & 干预措施
Rivastigmine
Rivastigmine, transdermal administration with a dosage of 4.6 and 9.6mg. The patches will be administered daily. The duration will equate to the duration of ECT treatment (that will be clinically determined)
干预措施: Rivastigmine Transdermal Product (Drug)
Sham
Non-active patches will be administered daily. The duration will equate to the duration of ECT treatment (that will be clinically determined)
干预措施: Sham (Other)
结局指标
主要结局
The effect of rivastigmine on scores of the verbal fluency test.
时间窗: Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session
Changes in cognitive functioning as measured by scores on the Verbal fluency test, in which participants are asked to pronounce as many words (0 - infinity) as possible in 60 seconds in a certain category or starting with a certain letter. A higher score means a better outcome.
The effect of rivastigmine on changes in scores on the Montreal Cognitive Assessment
时间窗: Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session
Changes in cognitive functioning as measured by scores on the Montreal Cognitive Assessment, that comprises of assessing multiple cognitive domains with a scoring scale of 0-30. A higher score means a better outcome.
The effect of rivastigmine on changes in scores on the Columbia University Autobiographical Memory Interview short form
时间窗: Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session
Changes in cognitive functioning before, during and after treatment as measured by scores on the Columbia University Autobiographical Memory Interviewshort form. The subject's ability to remember the specific details originally provided during the pre-treatment interview is measured on a scale of 0-60 points. A higher score means a better outcome.
Remission
时间窗: At 3-months after the last treatment session
with the Hamilton Depression Scale (17-item version), that comprises of 17 questions on depressive symptoms measured on a scale of 0-52 points. A higher score means a worse outcome.Remission as measured by a score of \<7.
The effect of rivastigmine on scores of the Rey auditory verbal learning test
时间窗: Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session
Changes in cognitive functioning as measured by scores on the Rey auditory verbal learning test, in which the assessor reads a list of of 15 words to the participant, and the participant is asked to repeat as many words as they remember. This is repeated 5 times (learning) and 15 minutes later the participant is asked how many words (0-15 words) they remember (memory). The scale ranges from 0-90 words in total. A higher score means a better outcome.
Changes in resting-state EEG peak frequency
时间窗: Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session
To develop an outcome prediction model the investigators will use resting state EEG output in units of peak frequency
Treatment response
时间窗: At 3-months after the last treatment session
Treatment response defined as 50% symptom reduction as measured with the Hamilton Depression Scale (17-item version), that comprises of 17 questions on depressive symptoms measured on a scale of 0-52 points. A higher score means a worse outcome.
次要结局
- Changes in the global assessment of disability using the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 12 item version(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Changes in behavioral outcome measured with the selective attention EEG task(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Quality of life of patients assessed with the visual analog scale of the European Quality of Life Five Dimensions with Five Levels (Euro-QoL-5D-5L)(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Quality of life of patients assessed with the European Quality of Life Five Dimensions with Five Levels (Euro-QoL-5D-5L)(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Changes in peak amplitude measured with selective attention EEG task(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Changes in processing negativity measured with the selective attention EEG task(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Change in subjective feeling of memory impairment on the Subjective Assessment of Memory Impairment (SAMI) questionnaire(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Changes in mismatch negativity measures (amplitude, latency and duration) obtained with the MisMatch Negativity Paradigm during an EEG recoding(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Change in impact of cognitive adverse events on the Subjective Assessment of Memory Impairment (SAMI) questionnaire(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
- Changes in the Expectation of response form(Baseline, within 72 hours after the first treatment session, within 1 week after the last treatment session and at 3-months after the last treatment session)
研究者
Iris Sommer
Professor
University Medical Center Groningen