Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine

NCT05768126 | Recruiting Phase 4 DMC

• 1 other identifier: 202000842
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Depressive Disorder

Keywords

electroconvulsive therapy; rivastigmine; EEG

Outcome Measures

Primary Outcomes (13)

• The effect of rivastigmine on scores of the verbal fluency test.

  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.

  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

• The effect of rivastigmine on scores of the Rey auditory verbal learning test

  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.

  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

• The effect of rivastigmine on changes in scores on the Montreal Cognitive Assessment

  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.

  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

• The effect of rivastigmine on changes in scores on the Columbia University Autobiographical Memory Interview short form

  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.

  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 resting-state EEG peak frequency

  To develop an outcome prediction model the investigators will use resting state EEG output in units of peak frequency

  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

• Treatment response

  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.

  Baseline

• Treatment response

  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.

  Within 72 hours after the first treatment session

• Treatment response

  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.

  Within 1 week after the last treatment session

• Treatment response

  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.

  At 3-months after the last treatment session

• Remission

  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.

  Baseline

• Remission

  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.

  Within 72 hours after the first treatment session

• Remission

  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.

  Within 1 week after the last treatment session

• Remission

  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.

  At 3-months after the last treatment session

Secondary Outcomes (10)

• 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

• 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

• 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 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 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

Other Outcomes (2)

• Changes in Free speech using the PRAAT 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 DNA methylation

  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

Study Arms (2)

Rivastigmine

EXPERIMENTAL

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)

Drug: Rivastigmine Transdermal Product

Sham

SHAM COMPARATOR

Non-active patches will be administered daily. The duration will equate to the duration of ECT treatment (that will be clinically determined)

Other: Sham

Interventions

Rivastigmine Transdermal Product DRUG

The patches will be administered (first four weeks 4.6 mg and then 9.5. mg).

Rivastigmine

Sham OTHER

The sham patches will be administered during the same period of time as the rivastigmine.

Sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• St. Antonius Hospital: collaborator
• Tergooi Hospital: collaborator

Study Sites (1)

UMC Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Depressive Disorder

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Iris EC Sommer, PhD, MD

  UMC Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jasper O. Nuninga, PhD

CONTACT

+31(6)39139525; j.o.nuninga@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: March 14, 2023
• Study Start: September 29, 2021
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: May 10, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)