Neuroimaging Predictors of Treatment Failure in Adult New-onset Epilepsy

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Capital District Health Authority, Canada
Sponsor:
Collaborator:
Nova Scotia Health Research Foundation
Information provided by (Responsible Party):
Bernd Pohlmann-Eden, Capital District Health Authority, Canada
ClinicalTrials.gov Identifier:
NCT01320670
First received: March 21, 2011
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

Epilepsy, defined as recurrent, unprovoked seizures, is a common condition, affecting 0.5-1% of the general population. People with uncontrolled epilepsy suffer poor health and increased mortality due to their condition. They frequently experience social stigma and are socioeconomically disadvantaged. It is therefore imperative to help them gain control of their seizures as quickly as possible. A wide range of antiepileptic drugs (AEDs) has become available to treat people with epilepsy. However, despite maximal therapy, approximately 20-40% show pharmacoresistance (PR) and thus continue to have seizures.

We do not understand why a significant proportion of people with epilepsy have PR. For any given patient presenting with a first unprovoked seizure, we are unable to predict PR at the time of presentation. At least 2 different AEDs must be tried at maximum doses for a year before we can diagnose PR. At this point, surgical therapies become an increasingly urgent consideration.

Retrospective magnetic resonance imaging (MRI) studies in the chronic stages of epilepsy have shown that patients with PR are more likely to have focal structural lesions in the brain, and in particular to have signs of damage to the hippocampi. For example, there are retrospective data suggesting that a decreased hippocampal N-acetylaspartate (NAA)/creatine ratio (measured by magnetic resonance spectroscopy [MRS]) and hippocampal atrophy (determined by hippocampal volumetry) correlate with PR. However, it is not clear whether these findings reflect the underlying pathophysiology of PR, or simply reflect the effects of chronic seizures and chronic drug treatment on the brain.

The First Seizure Clinic at the Halifax Infirmary represents a unique opportunity for prospective, longitudinal studies of patients who present with a first seizure or with newly diagnosed epilepsy. In these patients, advanced neuroimaging techniques at presentation might show changes that truly reflect the underlying pathophysiology of PR, rather than changes that develop as a consequence of prolonged seizures and drug treatment. Neuroimaging follow-up might help us to understand the pathophysiologic changes that accompany the evolution of PR. Ultimately, it is our hope to combine neuroimaging features and clinical features of patients with PR in a predictive model that would help us to predict PR at presentation.


Condition
Epilepsy
Seizures

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neuroimaging Predictors of Treatment Failure in Adult New-onset Epilepsy

Resource links provided by NLM:


Further study details as provided by Capital District Health Authority, Canada:

Primary Outcome Measures:
  • Pharmacoresistance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the study, each participant will be categorized as "PR" or "not PR" by the principal investigator. Participants will be categorized as PR if they have not achieved seizure freedom within 1 year of therapy, using at least 2 AEDs at maximal dose.


Secondary Outcome Measures:
  • Hippocampal NAA/creatine ratio [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Hippocampal NAA/creatine ratio will be determined by single voxel magnetic resonance spectroscopy.


Estimated Enrollment: 50
Study Start Date: June 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with first seizure or new-onset epilepsy aged > 17 years

Criteria

Inclusion Criteria:

  • Age 17 years
  • Newly diagnosed epilepsy or history of first unprovoked, witnessed seizure

Exclusion Criteria:

  • Lack of consent provoked seizure due to obvious
  • Acute lesion on CT (e.g. stroke, hemorrhage
  • Provoked seizure due to obvious, chronic lesion on CT (e.g. vascular malformation, tumour)
  • Progressive brain disease (e.g. neoplastic, infectious, demyelinating diseases)
  • History of epilepsy longer than 1 year at presentation to FSC
  • History of AED treatment for more than 4 weeks
  • Contraindication to MRI
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320670

Contacts
Contact: Bernhard Pohlmann-Eden, MD, PhD 902-473-1882 b.pohlmann-eden@dal.ca
Contact: Matthias H Schmidt, MD 902-473-5332 mhschmid@dal.ca

Locations
Canada, Nova Scotia
Halifax Infirmary Recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Contact: Bernhard Pohlmann-Eden, MD, PhD    902-473-1882    b.pohlmann-eden@dal.ca   
Contact: Matthias H Schmidt, MD    902-473-5332    mhschmid@dal.ca   
Principal Investigator: Bernhard Pohlmann-Eden, MD, PhD         
Sub-Investigator: Matthias H Schmidt, MD         
Sponsors and Collaborators
Capital District Health Authority, Canada
Nova Scotia Health Research Foundation
Investigators
Principal Investigator: Bernd Pohlmann-Eden, MD, PhD Capital Health, Canada
  More Information

Publications:
Responsible Party: Bernd Pohlmann-Eden, Professor, Capital District Health Authority, Canada
ClinicalTrials.gov Identifier: NCT01320670     History of Changes
Other Study ID Numbers: CDHA-RS/2011-258, 1164
Study First Received: March 21, 2011
Last Updated: January 17, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Capital District Health Authority, Canada:
pharmacoresistance

Additional relevant MeSH terms:
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on August 26, 2014