Measuring Blood Flow in the Brain After Epileptic Activity

NCT04028596 | Completed Phase 2 DMC

• 1 other identifier: NL68690.091.18
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Epilepsy; Depression; Postictal Delirium; Electroconvulsive Therapy

Keywords

Epilepsy; Depression; Electroconvulsive Therapy; Postictal; Clinical Trial; Postictal hypoperfusion/hypoxia

Outcome Measures

Primary Outcomes (1)

• Time to EEG normalization

  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 Outcomes (5)

• Postictal reorientation time (by Sobin, 1995)

  immediately after each ECT session, up to 12 times per patient (across 6 weeks)

• Structural MRI

  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

  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

  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

  baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min.

Study Arms (3)

Acetaminophen

ACTIVE COMPARATOR

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

Nimodipine

ACTIVE COMPARATOR

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

Control

NO INTERVENTION

Glass of water (50cc) only. Once 2h before the ECT-session. Total maximum of five times over the course of weeks.

Interventions

Paracetamol DRUG

once, 1000mg, 2 h before ECT session

Also known as: RVG 107336

Acetaminophen

Nimotop DRUG

once, 60mg, 2 h before ECT session

Also known as: RVG 12060

Nimodipine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Rijnstate Hospital: lead
• University of Twente: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Rijnstate Hospital

Arnhem, Gelderland, 6815 AD, Netherlands

Location

Related Publications (8)

• Farrell JS, Gaxiola-Valdez I, Wolff MD, David LS, Dika HI, Geeraert BL, Rachel Wang X, Singh S, Spanswick SC, Dunn JF, Antle MC, Federico P, Teskey GC. Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent. Elife. 2016 Nov 22;5:e19352. doi: 10.7554/eLife.19352.

  PMID: 27874832 BACKGROUND

• Farrell JS, Colangeli R, Wolff MD, Wall AK, Phillips TJ, George A, Federico P, Teskey GC. Postictal hypoperfusion/hypoxia provides the foundation for a unified theory of seizure-induced brain abnormalities and behavioral dysfunction. Epilepsia. 2017 Sep;58(9):1493-1501. doi: 10.1111/epi.13827. Epub 2017 Jun 20.

  PMID: 28632329 BACKGROUND

• Fisher RS, Schachter SC. The postictal state: a neglected entity in the management of epilepsy. Epilepsy Behav. 2000 Feb;1(1):52-9. doi: 10.1006/ebeh.2000.0023.

  PMID: 12609127 BACKGROUND

• Hansson L, Hedner T, Dahlof B. Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press. 1992 Aug;1(2):113-9. doi: 10.3109/08037059209077502.

  PMID: 1366259 BACKGROUND

• Krauss G, Theodore WH. Treatment strategies in the postictal state. Epilepsy Behav. 2010 Oct;19(2):188-90. doi: 10.1016/j.yebeh.2010.06.030. Epub 2010 Aug 17.

  PMID: 20719574 BACKGROUND

• Sobin C, Sackeim HA, Prudic J, Devanand DP, Moody BJ, McElhiney MC. Predictors of retrograde amnesia following ECT. Am J Psychiatry. 1995 Jul;152(7):995-1001. doi: 10.1176/ajp.152.7.995.

  PMID: 7793470 BACKGROUND

• Pottkamper JCM, Verdijk JPAJ, Stuiver S, Doesschate FT, van Putten MJAM, Hofmeijer J, van Waarde JA, van Wingen GA. Postictal resting-state connectivity changes after electroconvulsive therapy-induced seizures. Eur Arch Psychiatry Clin Neurosci. 2025 Jul 14. doi: 10.1007/s00406-025-02043-7. Online ahead of print.

  PMID: 40659830 DERIVED

• Verdijk JPAJ, Pottkamper JCM, Verwijk E, van Wingen GA, van Putten MJAM, Hofmeijer J, van Waarde JA. Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE). Trials. 2022 Apr 18;23(1):324. doi: 10.1186/s13063-022-06206-y.

  PMID: 35436940 DERIVED

MeSH Terms

Conditions

Epilepsy; Depression; Hypoxia

Interventions

Acetaminophen; Nimodipine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Behavioral Symptoms; Behavior; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids

Study Officials

• Jeroen A van Waarde, MD

  Rijnstate Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The PROBE design will be used in this study, in which the principal investigator will be blinded to the administration of drugs until the end of the study. The other principal investigator will know about administration, but will not be involved in testing patients.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study makes use of a 3 x 3 crossover design, in which patients receive a randomized sequence of interventions in pairs of 3 (acetaminophen, nimodipine, no intervention), with a maximum of 12 interventions/measurements.

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 22, 2019
• Study Start: December 5, 2019
• Primary Completion: December 30, 2022
• Study Completion: April 15, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• 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).
• Access Criteria: Data will be shared with experienced data analysts at the Amsterdam UMC (MRI analyses).

Locations

NL (1)