Measuring Blood Flow in the Brain After Epileptic Activity

Depression Clinical Trial

— SYNAPSE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04028596
• Other study ID #: NL68690.091.18
• Status: Completed
• Phase: Phase 2
• 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
• 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;

Related Conditions & MeSH terms

• Depression
• Electroconvulsive Therapy
• Epilepsy
• Postictal Delirium

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.