Clinical trial NCT02126774: The Human Epilepsy Project
Official title: The Human Epilepsy Project
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Focal Epilepsy
Keywords: epilepsy
focal epilepsy
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: The Epilepsy Study Consortium
First posted: 2014-04-30
Enrollment: 488
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Epilepsy/Neurology clinical centers

Brief summary: HEP is a five-year, prospective, observational study whose primary goal is to identify clinical characteristics and biomarkers predictive of disease outcome, progression, and treatment response in participants with newly treated focal epilepsy.

Detailed description: Epilepsy is a serious disease. It affects approximately 2.4 million Americans, with a lifetime risk estimated at 3%. More than 181,000 Americans develop epilepsy every year, and a substantial proportion has seizures that cannot be controlled by available medications. For the vast majority of patients with epilepsy, we do not understand the biological basis of their disease; we do not know whether a given anti-epileptic drug (AED) will be effective; and we cannot predict the severity of the seizure disorder, the potential emergence of co-morbidities, or the likelihood of remission.

The Human Epilepsy Project seeks to answer these unknowns by collecting high-resolution clinical information and treatment response, MRIs, EEGs, and blood and urine samples for biomarkers. A major outcome of the project is to create an open data repository of clinical information and biologic samples for future studies.

HEP may have a transformative impact on epilepsy diagnosis and treatment by identifying critical clinical features and biomarkers at the onset of epilepsy that can be used to predict outcome and guide therapy. We hope to identify subsets of patients at high risk for pharmacoresistance who may benefit from more aggressive initial therapy and earlier consideration for surgical treatment. The existence of biomarkers that predict the likelihood of disease remission would dramatically affect treatment decisions and counseling for millions of patients.

In addition to its impact on current clinical care, the data and specimens collected in HEP, including sequential neuroimaging, electrophysiology and metabolite profiles, and banked DNA for the purpose of future genomics studies, have the potential to provide new insights into the biological basis of focal epilepsy, which will advance our efforts to discover effective treatments and cures for this disorder.

Eligibility criteria: Inclusion Criteria:

* Clinical seizure(s) and history consistent with focal epilepsy
* At least two confirmed spontaneous seizures, at least 24 hours apart, in the 12 months prior to enrollment
* Complete AED history prior to enrollment (with approximate dates and doses) is available (exception can be made for AEDs taken for \<1 week)
* Age ≥12 years and ≤60 years at time of seizure onset
* Age ≥12 years and ≤60 years at time of enrollment
* Treatment instituted not more than 4 months prior to enrollment
* One of the following:

  1. Normal MRI with inter-ictal EEG showing focal abnormality (focal sharp waves or focal slowing)
  2. Normal MRI and normal inter-ictal EEG, with clinical or electrographic seizure activity on ictal EEG
  3. Definitive clinical history of recurrent seizures consistent with focal epilepsy, adjudicated by central reviewers, if normal MRI and normal EEG
  4. Focal lesion (non-progressive) on MRI with normal EEG (acceptable focal lesions include MTS, FCD, single cavernoma, and AVMs that are not of large size and lack significant amounts of hemosiderin)

Exclusion Criteria:

* Idiopathic or symptomatic generalized epilepsy
* Any epilepsy etiology that could produce significant gliosis or brain injury and would be likely to alter biomarkers. These include:

  1. Epilepsy with an etiology occurring in the previous two years that would produce significant CNS injury (e.g., traumatic brain injury that involves direct disruption of brain tissue, stroke, encephalitis)
  2. History of intracranial bleeding (e.g., subarachnoid, intraparenchymal)
* Identified genetic epilepsy syndrome
* Presence of moderate or greater developmental or cognitive delay prior to seizure onset (e.g., if an adolescent, not in self-contained classroom; if IQ is documented, should be \> 70)
* History of chronic drug or alcohol abuse within the last 2 years
* IGE/focal epilepsy mixed syndromes
* Progressive neurological disorder (brain tumor, AD, PME, etc.)
* Major medical co-morbidities such as renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease
* Autism Spectrum Disorder
* Seizures only during pregnancy
* History of previous or current significant psychiatric disorder that would interfere with conduct of the study

Primary outcomes:
measure: Presence of Biomarker(s) Predictive of Anti-epileptic Drug Treatment Response
timeFrame: up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Great Neck
country: United States
facility: North Shore-LIJ Health System
state: New York
city: New York
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Melbourne
country: Australia
facility: Austin Hospital, University of Melbourne
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Sydney
country: Australia
facility: Prince of Wales Hospital, University of New South Wales
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
Study officials:
affiliation: New York University, Comprehensive Epilepsy Center
name: Ruben Kuzniecky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York University, Comprehensive Epilepsy Center
name: Jacqueline French, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco, Department of Neurology
name: Daniel Lowenstein, MD
role: PRINCIPAL_INVESTIGATOR
References: