Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural Hematomas

NCT ID: NCT04759196

Last Updated: 2021-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-01

Study Completion Date

2024-12-31

Brief Summary

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Some patients with chronic subdural hematomas and transient neurological symptoms do not respond to standard antiepileptic drugs. The investigators think that some of them could have cortical depression rather than epileptic discharges. After an intensive literature review, the investigators found out that some antiepileptic dugs (Lamotrigine, Topiramate) were found to be efficient to treat cortical depression in other conditions (migraine, subarachnoid hemorrhage). In contrast, some other drugs (Levetiracetam) were not proved to be efficient. Knowing that, the investigators want to compare the efficacy of Topiramate against Levetiracetam in two different groups, the NESIS group (based on a NESIS score of 4 or more - increased risk of cortical depression) versus a non-NESIS group (score of 3 or less - increased risk of epileptic discharges).

Detailed Description

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Patients presenting with transient neurological symptoms in the context of subdural hemorrhage may present a diagnostic challenge. Many of these patients end up with a probable diagnosis of epilepsy (or acute symptomatic seizures), despite a negative electroencephalogram. The investigators believe that the origin of these transient neurologic symptoms in a significant subpopulation of these patients may in fact be cortical depolarization, rather than epileptiform activity. Very specific characteristics have already been identified that differentiate these patients from those who ultimately have epilepsy. The NESIS entity (nonepileptic, stereotypical, and intermittent symptoms) has been proposed to represent this group of patients. A NESIS score was then designed to help distinguish patients with epileptiform activity (confirmed by EEG) from those likely to have cortical depolarization. In other diseases presenting cortical depolarizations, certain antiepileptic treatments (including Topiramate) have already been recognized as effective. The investigators therefore want to perform a prospective, multicenter, randomized-controlled study (Topiramate group and Levetiracetam group) to determine whether a significant difference in the response to treatment exists between Topiramate and Levetiracetam in the NESIS group compared to the non-NESIS group. In addition, in a few eligible patients, the investigators will implant an electrocorticography electrode to demonstrate the existence of cortical depolarizations.

Conditions

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Chronic Subdural Hematoma Epilepsy; Seizure Cortical Depression; Cortical Depolarization Nonepileptic, Stereotypical and Intermittent Symptoms NESIS

Keywords

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Transient neurological symptoms Levetiracetam; keppra Lamotrigine; lamictal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients with chronic subdural hematomas, transient neurological symptoms with negative EEG will be divided in two groups based on their NESIS scores (up to 3 (increased risk of epileptic seizures) and 4 or more (increased risk of cortical depression)). Those two groups are going to receive both Levetiracetam or Lamotrigine.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Caregivers Outcome Assessors
The participant will not know the medication they are taking. When accepting to participate, they are going to have the full list of possible side effects, without knowing which one are link to which medication.

The doctors in charge of administering the questionnaires will be blind. The person in charge of analyzing the results will also be blind.

Study Groups

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NESIS - Levetiracetam

Participant with a score NESIS of 4 or more (increased risk of having cortical depression).

Levetiracetam is an anti-epileptic drug known to be inefficient in other condition with cortical depression. It will be use as an active comparator.

Group Type ACTIVE_COMPARATOR

Levetiracetam

Intervention Type DRUG

LEV : 500 mg BID, with increase of 1000 mg die divided in two doses each week until efficacy, to a maximum of 1500 mg BID.

NESIS - Topiramate

Participant with a score NESIS of 4 or more (increased risk of having cortical depression).

Topiramate is an anti-epileptic drug known to be efficient in other condition with cortical depression. The investigators want to test his efficacy in chronic subdural hematoma with probable cortical depression.

Group Type EXPERIMENTAL

Topamax

Intervention Type DRUG

TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.

Non NESIS - Levetiracetam

Participant with a score NESIS of 3 or less (increased risk of having epileptic discharges).

Levetiracetam is an anti-epileptic drug known to be inefficient in other condition with cortical depression. It will be use as an active comparator.

Levetiracetam should be as efficient as Topiramate in a group a participant with epileptic discharges.

Group Type ACTIVE_COMPARATOR

Levetiracetam

Intervention Type DRUG

LEV : 500 mg BID, with increase of 1000 mg die divided in two doses each week until efficacy, to a maximum of 1500 mg BID.

Non-NESIS - Topiramate

Participant with a score NESIS of 3 or less (increased risk of having epileptic discharges).

Topiramate is an anti-epileptic drug known to be efficient in other condition with cortical depression. The investigators want to test his efficacy in chronic subdural hematoma with probable cortical depression.

Topiramate should be as efficient as Levetiracetam in a group a participant with epileptic discharges.

Group Type EXPERIMENTAL

Topamax

Intervention Type DRUG

TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.

Interventions

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Topamax

TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.

Intervention Type DRUG

Levetiracetam

LEV : 500 mg BID, with increase of 1000 mg die divided in two doses each week until efficacy, to a maximum of 1500 mg BID.

Intervention Type DRUG

Other Intervention Names

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Topiramate TPM LEV Keppra

Eligibility Criteria

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Inclusion Criteria

* Be aged ≥ 18 years
* Chronic subdural hematoma
* Transient neurological symptoms (Sensory, motor, cerebellar or speech symptoms, lasting 6 hours or less)
* Initial negative EEG

Exclusion Criteria

* Contraindications to Levetiracetam
* Psychiatric history (major depression, psychosis, risk of suicide)
* History of hypersensitivity to LEV (anaphylaxis, angioedema, skin reaction)
* Contraindications to Topiramate
* History of hypersensitivity to TPM
* Glaucoma
* Past of nephrolithiasis
* Known epilepsy or past seizure before the current subdural hemorrhage
* Actual taking of an antiepileptic drug
* Intracranial pathology not caused by subdural hematoma (intra-parenchymal hemorrhage, neoplasia)
* Pregnancy or planning to
* Inability to carry out the necessary follow-ups for the study
* Refusal of the attending physician
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Université de Sherbrooke

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christian Iorio-Morin, MD

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Locations

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Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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suzie adam, MD

Role: CONTACT

Phone: 5146990518

Email: [email protected]

Mathieu Lévesque, MD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Christian Iorio-Morin, MD, PhD

Role: primary

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Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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MP-31-2021-3687

Identifier Type: -

Identifier Source: org_study_id