Measuring Blood Flow in the Brain After Epileptic Activity (SYNAPSE)

November 15, 2023 updated by: Rijnstate Hospital

StudY of Effect of Nimodipine and Acetaminophen on Postictal Symptoms After ECT

In this clinical trial, postictal phenomena (i.e., headache, delirium) will be investigated after administration of acetaminophen and nimodipine in depressed patients receiving electroconvulsive therapy (ECT). Postictal phenomena are thought to result from decreased cerebral blood flow and decreased oxygen concentration in the brain. It is expected that acetaminophen and nimodipine will reduce these postictal phenomena, compared to no treatment, because they target these mechanisms.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Postictal phenomena, such as sensory, motor or memory deficits, headache, delirium, and psychosis, are common manifestations after electroconvulsive therapy (ECT) induced seizures. Also, postictal phenomena add to the burden of seizures in patients with epilepsy. The pathophysiology of these phenomena is poorly understood and effective treatments are not available (Fisher RS, 2000; Krauss & Theodore, 2010). Recently, seizure-induced postictal vasoconstriction with cerebral hypoperfusion was observed in experimentally induced seizures in rats. Treatment with acetaminophen or calcium antagonists decreased hypoperfusion and postictal phenomena (Farrell, 2016, 2017).

The objective of this research is to study the effect of acetaminophen and nimodipine to reduce postictal phenomena after ECT induced seizures.

A prospective, three conditions crossover trial will be conducted, with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design; Hansson, Hedner, & Dahlof, 1992).

Thirty-three adult (age >17 years) patients referred to treatment with ECT for a depressive episode will be included to achieve a statistical power of .80. This will be feasible in one year.

A single dose of nimodipine (60 mg) or acetaminophen (1000 mg) or no additional treatment will be given prior to a maximum of 12 ECT-sessions per patient. Patients will be randomly assigned to predefined treatment sequences. EEG and MRI measures will serve as main outcome measures, as well as psychometric tests.

Data will be stored on two separate hard disks, one including patient sensitive information for identification, the other with anonymized data only (for the sponsor).

Patients will be recruited by doctors at Rijnstate Hospital Arnhem. A mixed model with repeated measurements analysis will be conducted for the primary outcome measures.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Gelderland
      • Arnhem, Gelderland, Netherlands, 6815 AD
        • Rijnstate Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adulthood (age > 17 years);
  • Current clinical diagnosis of depressive episode (unipolar, bipolar, schizoaffective);
  • Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements.

Exclusion Criteria:

  • Known adverse or allergic reactions to acetaminophen or nimodipine;
  • Chronic use of acetaminophen, calcium-antagonists or NSAID's that cannot be interrupted for less than two days before the ECT-session;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Acetaminophen
Trade name: Paracetamol Pharmaceutical form: Tablet (oral use) Once 1000 mg 2h before the ECT-session. Total maximum of five times over the course of weeks
Drug: Paracetamol
once, 1000mg, 2 h before ECT session
Other Names:
  • RVG 107336
Active Comparator: Nimodipine
Trade name: Nimotop Pharmaceutical form: Film-coated tablet (oral use) Once 60mg 2h before the ECT-session. Total maximum of five times over the course of weeks.
Drug: Nimotop
once, 60mg, 2 h before ECT session
Other Names:
  • RVG 12060
No Intervention: Control
Glass of water (50cc) only. Once 2h before the ECT-session. Total maximum of five times over the course of weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to EEG normalization
Time Frame: Change from ictal to baseline EEG activity, up to 12 times per patient (across 6 weeks)
quantitative metric of EEG background evolution over time, in seconds (will be assessed at baseline, during electroconvulsive therapy, and immediately afterwards for approximately 1 hour)
Change from ictal to baseline EEG activity, up to 12 times per patient (across 6 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postictal reorientation time (by Sobin, 1995)
Time Frame: immediately after each ECT session, up to 12 times per patient (across 6 weeks)
Five questions regarding reorientation will be asked in an interval of 5 minutes after electroconvulsive shock therapy has ended. If the patient can answer 4 out of the 5 questions correctly, this is determined as the final score (in minutes). The scale ranges from 5 to 100 minutes. These scores indicate the time frame a patient needs until he/she is fully conscious and reoriented. Higher values indicate that a patient needs more time to regain reorientation.
immediately after each ECT session, up to 12 times per patient (across 6 weeks)
Structural MRI
Time Frame: baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.
Isovoxel T1-weighted data (to make volumetric changes); is part of the MRI sequence (takes in total approximately 25 minutes)
baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.
Arterial Spin Labeling MRI
Time Frame: baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 7 min.
measures cerebral perfusion levels
baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 7 min.
Resting state functional MRI
Time Frame: baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.
used for brain mapping, measures functional organization (and connectivity) of certain brain areas
baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.
Diffusion Tensor Imaging
Time Frame: baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.
measures diffusion in the brain to estimate the axonal organization of the brain
baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rijnstate Hospital

Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
University of Twente

Investigators

  • Principal Investigator: Jeroen A van Waarde, MD, Rijnstate Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2019

Primary Completion (Actual)

December 30, 2022

Study Completion (Actual)

April 15, 2023

Study Registration Dates

First Submitted

July 8, 2019

First Submitted That Met QC Criteria

July 19, 2019

First Posted (Actual)

July 22, 2019

Study Record Updates

Last Update Posted (Estimated)

November 16, 2023

Last Update Submitted That Met QC Criteria

November 15, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL68690.091.18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The EEG, MRI, and psychometric data will be shared with the University of Twente and the Amsterdam UMC. All patient data will be anonymized so that it cannot be connected to the patients. Demographic data will also be included in these files and anonymized.

IPD Sharing Time Frame

Data will be archived for 15 years (according to the standard practice of Rijnstate Hospital). Data will become available as of the last date of testing (approx. December 2020).

IPD Sharing Access Criteria

Data will be shared with experienced data analysts at the Amsterdam UMC (MRI analyses).

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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