Primary research question:- Does treatment with drugs modulating vasoconstriction, i.e. COX-inhibitors (acetaminophen) or calcium-antagonists (nimodipine), improve electrographic postictal phenomena?Secondary research questions:- Does treatment with…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure will be *time to EEG normalization*, defined as the
time interval between seizure onset and return to the pre-ECT (baseline) EEG,
quantified with the temporal Brain Symmetry Index.
Secondary outcome
Clinical measures :
- *Orientation recovery time*, defined as the time-interval between seizure
onset and orientation in time, person, and place.
- The incidence and severity of headache, nausea and myalgia as measured using
a visual analogue scale.
EEG measures:
- The alpha/delta ratio derived from the EEG as a function of time after ECT.
This ratio will be fitted to a sigmoid function, allowing to extract the
*postictal recovery time constant (PRTC)*.
- The cerebral recovery index (CRI) which is based on the evolution of several
qEEG features over time.
MRI measures within one hour after seizure termination. Patients will undergo
MRI scans after each of three ECT-sessions from one condition sequence, so that
from each patient at least one MRI is collected with every condition:
- Cerebral perfusion: MRI with Arterial Spin Labeling (pCASL sequence on 3T
Philips scanner) will be used measure perfusion levels.
- Vessel diameter as measured with MRA.
- Resting state activity and functional connectivity as measured by BOLD fMRI.
- Structural MRI will be collected using isovoxel T1-weighted data to make
volumetric changes during the ECT-course possible.
- Diffusion Tensor Imaging data will be collected to analyse tractographic
changes during the ECT-course.
Background summary
Postictal phenomena, such as sensory, motor or memory deficits, headache,
delirium and psychosis, are common manifestations after epileptic and
electroconvulsive therapy (ECT) induced seizures and add to the burden of
disease. The pathophysiology of these phenomena are poorly understood and
specific treatments are not available. Recently, seizure induced postictal
vasoconstriction with hypoperfusion was observed in experimentally induced
seizures in rats. Treatment with acetaminophen or calcium antagonists decreased
hypoperfusion and postictal phenomena.
Study objective
Primary research question:
- Does treatment with drugs modulating vasoconstriction, i.e. COX-inhibitors
(acetaminophen) or calcium-antagonists (nimodipine), improve electrographic
postictal phenomena?
Secondary research questions:
- Does treatment with acetaminophen or nimodipine improve *time to orientation*?
- Does treatment with paracetamol or nimodipine prevent or limit postictal
hypoperfusion?
- Are clinical and electrographic postictal phenomena associated with
hypoperfusion?
Study design
A prospective, three conditions cross over trial, with randomised condition
allocation, open-label, and blinded end-point evaluation (PROBE design).
Intervention
A single dose of nimodipine (60 mg) or acetaminophen (1000 mg) or no additional
treatment will be given prior to each ECT-session. Patients will be randomly
assigned to predefined treatment sequences.
Study burden and risks
Acetaminophen (Paracetamol) is a widely used analgesic drug. A single dose of
1000mg has no relevant side effects. Nimodipine in a dose of 60mg, 6 times
daily during three weeks, is part of standard treatment for prevention of
vasoconstriction in patients with subarachnoid haemorrhage and generally well
tolerated. A single dose of 60mg may in a few cases cause a temporary reduction
in blood pressure. Since this treatment is administered in the
highly-controlled environment of an operation theatre, where ECT takes place,
we consider this associated risk as negligible. MRI scanning and cognitive
evaluation shortly after the ECT-session may be perceived as inconvenient by
some patients, but we foresee no relevant additional risks. Important possible
benefits include a reduction of postictal symptoms with acetaminophen or
nimodipine treatment in the future.
Wagnerlaan 55
Arnhem 6815AD
NL
Wagnerlaan 55
Arnhem 6815AD
NL
Listed location countries
Age
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 reactions to acetaminophen or nimodipine. In that case
participants can still be included into the other intervention groups;
Chronic use of acetaminophen, calcium-antagonists or NSAID*s that cannot be
interrupted for less than two days before the ECT-session.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | 7718 |
| EudraCT | EUCTR2019-000617-37-NL |
| CCMO | NL68690.091.19 |
| OMON | NL-OMON26656 |