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

April 27, 2021 updated by: Université de Sherbrooke
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

56

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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.
Other Names:
  • Keppra
  • LEV
Experimental: 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.
Drug: Topamax
TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.
Other Names:
  • Topiramate
  • TPM
Active Comparator: 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.
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.
Other Names:
  • Keppra
  • LEV
Experimental: 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.
Drug: Topamax
TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.
Other Names:
  • Topiramate
  • TPM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Between-group difference in the number of TNS reported at 6 month in participants with a positive Nonepileptic, Stereotyped, Intermittent Symptoms (NESIS) score (4 and more)
Time Frame: Through study completion, an average of 3 years
The aim of this study is to demonstrate the efficacy of Topiramate in the treatment of patients with transient neurological symptoms in the context of chronic subdural hemorrhage with a positive NESIS score (4 and more), in whom usual epilepsy treatment appears to be less effective. To do this, the effect of Topiramate (shown to be effective in cortical depressions) will be compared with that of Levetiracetam (which has not been shown to be effective in cortical depressions). This is going to be done by a questionnaire that will assess the resolution of symptoms or not, or the percentage of diminution.
Through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Between-group difference in the number of TNS reported at 6 month in all participants (all NESIS scores)
Time Frame: Through study completion, an average of 3 years
If the investigators manage to demonstrate a significant difference between the response to TPM and LEV in the NESIS group compared to the non-NESIS group with our questionnaire, the evidence concerning the existence of a different process at the origin of the NESIS group will then be more numerous. As demonstrated in studies on rats, cortical spreading depolarization respond well to TPM and not to LEV. Cortical depolarizations will then be the main hypothesis of the reason why some responds better to TPM than LEV in our study.
Through study completion, an average of 3 years
Incidence of cortical spreading depression on electrocorticography in the first postoperative week of patients with preoperative TNS.
Time Frame: Through study completion, an average of 3 years
The investigators think that cortical depression rather then epileptic discharges could be involved in some patients with transient neurological symptoms in context of subdural hematomas. Some participant could need decompression surgery for their subdural hematoma. The investigators will offer the insertion of electrocorticography electrods while this surgery. The aim of this intervention will be to prove cortical depression in some subjects by using electrocorticography that will be read by a neurologist specialized in epilepsy.
Through study completion, an average of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Université de Sherbrooke

Investigators

  • Principal Investigator: Christian Iorio-Morin, MD, Université de Sherbrooke

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

October 27, 2020

First Submitted That Met QC Criteria

February 15, 2021

First Posted (Actual)

February 18, 2021

Study Record Updates

Last Update Posted (Actual)

April 30, 2021

Last Update Submitted That Met QC Criteria

April 27, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MP-31-2021-3687

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Epilepsy; Seizure

Clinical Trials on Levetiracetam

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uganda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe