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Trial record 36 of 36 for:    fmri headache

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

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ClinicalTrials.gov Identifier: NCT04028596
Recruitment Status : Not yet recruiting
First Posted : July 22, 2019
Last Update Posted : July 22, 2019
Sponsor:
Collaborators:
University of Twente
Amsterdam University Medical Center
Information provided by (Responsible Party):
Rijnstate Hospital

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.

Condition or disease Intervention/treatment Phase
Epilepsy Depression Postictal Delirium Electroconvulsive Therapy Drug: Paracetamol Drug: Nimotop Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Single (Investigator)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: StudY of Effect of Nimodipine and Acetaminophen on Postictal Symptoms After ECT
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nimodipine

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 Name: 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 Name: 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.



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Postictal reorientation time (by Sobin, 1995) [ Time Frame: in the first hour after electroconvulsive therapy (once per intervention), up to 12 times per patient (across 6 weeks) ]
    Five questions regarding reorientation will be asked in an interval of 5 minutes after electronvulsive 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 patients needs more time to regain reorientation.

  2. Structural MRI [ Time Frame: in the first hour after electroconvulsive therapy (once per intervention, in total 3 times per participant), lasts approx. 5 min. ]
    Isovoxel T1-weighted data (to make volumetric changes); is part of the MRI sequence (takes in total approximately 25 minutes)

  3. Arterial Spin Labeling MRI [ Time Frame: in the first hour after electroconvulsive therapy (once per intervention, in total 3 times per participant), lasts approx. 7 min. ]
    measures cerebral perfusion levels

  4. Resting state functional MRI [ Time Frame: in the first hour after electroconvulsive therapy (once per intervention, in total 3 times per participant), lasts approx. 5 min. ]
    used for brain mapping, measures functional organization (and connectivity) of certain brain areas

  5. Magnetic resonance angiography [ Time Frame: in the first hour after electroconvulsive therapy (once per intervention, in total 3 times per participant), lasts approx. 5 min. ]
    measures the vessel diameter



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;
  • Contraindications for magnetic resonance imaging (e.g. ferromagnetic implants, pacemakers, claustrophobia)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028596


Contacts
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Contact: Joey Verdijk, MD 0031 880057766 jverdijk@rijnstate.nl
Contact: Julia Pottkämper, Msc 0031 534898525 j.c.m.pottkaemper@utwente.nl

Sponsors and Collaborators
Rijnstate Hospital
University of Twente
Amsterdam University Medical Center
Investigators
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Principal Investigator: Michel van Putten, MD University of Twente

Publications:
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Responsible Party: Rijnstate Hospital
ClinicalTrials.gov Identifier: NCT04028596     History of Changes
Other Study ID Numbers: NL68690.091.18
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Clinical Study Report (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).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rijnstate Hospital:
Epilepsy
Depression
Electroconvulsive Therapy
Postictal
Clinical Trial
Postictal hypoperfusion/hypoxia
Additional relevant MeSH terms:
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Epilepsy
Delirium
Depression
Behavioral Symptoms
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Neurocognitive Disorders
Acetaminophen
Nimodipine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Vasodilator Agents