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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04028596
Other study ID # NL68690.091.18
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date December 5, 2019
Est. completion date April 15, 2023

Study information

Verified date November 2023
Source Rijnstate Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 34
Est. completion date April 15, 2023
Est. primary completion date December 30, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Paracetamol
once, 1000mg, 2 h before ECT session
Nimotop
once, 60mg, 2 h before ECT session

Locations

Country Name City State
Netherlands Rijnstate Hospital Arnhem Gelderland

Sponsors (3)

Lead Sponsor Collaborator
Rijnstate Hospital Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Twente

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Postictal reorientation time (by Sobin, 1995) 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)
Secondary Structural MRI 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.
Secondary Arterial Spin Labeling MRI 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.
Secondary Resting state functional MRI 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.
Secondary Diffusion Tensor Imaging 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.
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