Clinical trial NCT05768126: Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine
Official title: Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Depressive Disorder
Keywords: electroconvulsive therapy
rivastigmine
EEG
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: St. Antonius Hospital
name: Tergooi Hospital
First posted: 2023-03-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The effect of rivastigmine on scores of the verbal fluency test.
timeFrame: 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
measure: The effect of rivastigmine on scores of the Rey auditory verbal learning test
timeFrame: 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
measure: The effect of rivastigmine on changes in scores on the Montreal Cognitive Assessment
timeFrame: 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
measure: The effect of rivastigmine on changes in scores on the Columbia University Autobiographical Memory Interview short form
timeFrame: 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
measure: Changes in resting-state EEG peak frequency
timeFrame: 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
measure: Treatment response
timeFrame: Baseline
measure: Treatment response
timeFrame: Within 72 hours after the first treatment session
measure: Treatment response
timeFrame: Within 1 week after the last treatment session
measure: Treatment response
timeFrame: At 3-months after the last treatment session
measure: Remission
timeFrame: Baseline
measure: Remission
timeFrame: Within 72 hours after the first treatment session
measure: Remission
timeFrame: Within 1 week after the last treatment session
measure: Remission
timeFrame: At 3-months after the last treatment session
Secondary outcomes:
measure: Quality of life of patients assessed with the European Quality of Life Five Dimensions with Five Levels (Euro-QoL-5D-5L)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Changes in the global assessment of disability using the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 12 item version
timeFrame: 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
measure: Changes in peak amplitude measured with selective attention EEG task
timeFrame: 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
measure: Changes in behavioral outcome measured with the selective attention EEG task
timeFrame: 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
measure: Changes in processing negativity measured with the selective attention EEG task
timeFrame: 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
measure: Changes in mismatch negativity measures (amplitude, latency and duration) obtained with the MisMatch Negativity Paradigm during an EEG recoding
timeFrame: 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
measure: Change in subjective feeling of memory impairment on the Subjective Assessment of Memory Impairment (SAMI) questionnaire
timeFrame: 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
measure: Change in impact of cognitive adverse events on the Subjective Assessment of Memory Impairment (SAMI) questionnaire
timeFrame: 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
measure: Changes in the Expectation of response form
timeFrame: 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
Other outcomes:
measure: Changes in Free speech using the PRAAT task
timeFrame: 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
measure: Changes in DNA methylation
timeFrame: 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
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Groningen
name: Iris EC Sommer, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: