Human Epilepsy Project 3 (HEP3)

NYU Langone Health

Status: Active, not recruiting

Conditions: Idiopathic Generalized Epilepsy

Study type: Observational

Funder types: Other

Identifiers

NCT05374928

19-01030

Details and patient eligibility

About

By carrying a careful, large-scale and ambitious prospective study of a cohort of participants with generalized epilepsy, the study team hopes to clarify the likelihood of response and remission in this type of epilepsy, and try to explore the underlying biological drivers of treatment response, including novel realms of exploration such as impact of the microbiome, and genetics. The identification of biomarkers that predict the likelihood of disease response would allow epilepsy patients to make more informed decisions about the factors affecting their quality of life, including plans for driving, relationships, pregnancy, schooling, work, and play. In addition to its impact on clinical care, the data and specimens collected in HEP3, including sequential electrophysiology, biochemical profiles and neuroimaging and banked DNA for future genomics studies, have the potential to provide new insights into the biological basis of IGE, thereby advancing the discovery of effective treatments and cures. By enrolling both newly diagnosed subjects (prognosis unknown) as well as subjects with established IGE who are already determined to be treatment resistant or treatment responsive, the study team can immediately test potential biomarkers in a confirmation cohort, which will accelerate identification of predictive biomarkers.

Enrollment: 320 patients

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Cohort 1: Newly Diagnosed IGE

Inclusion criteria:

1. Age ≥13 years at time of enrollment

2. Age ≥8 years at time of seizure onset

3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions

4. Occurrence of at least 1 seizure of any type in the 6 months prior to treatment

5. Patients must have one of the following:

   • GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   • GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   • GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   • A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review

6. Availability of a complete medication history since initiation of treatment, including doses and date of initiation

7. No competing cause of epilepsy (e.g. traumatic brain injury)

8. AED treatment (for seizures) instituted not more than 12 months before enrollment

Exclusion Criteria

1. Focal epilepsy
2. Generalized/focal epilepsy mixed syndromes
3. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
4. Epileptic or developmental encephalopathy
5. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
6. Autism Spectrum Disorder
7. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
8. Seizures only during pregnancy
9. History of previous or current significant psychiatric disorder that would interfere with study requirements

Cohort 2: Longstanding Treatment Responsive

Inclusion Criteria:

1. Age ≥13 years at time of enrollment

2. Age ≥8 years at time of seizure onset

3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions

4. Patients must have had one of the following:

   1. GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   2. GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   3. GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   4. A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review

5. Availability of a complete medication history since initiation of treatment, including doses and date of initiation

6. No competing cause of epilepsy (e.g. traumatic brain injury)

7. Two years of well-controlled seizures.

   1. No convulsive seizures in the last two years
   2. Myoclonic or absence seizures must be rare (<2 per year) and non-disabling
   3. Ongoing therapy with > 1 antiseizure medication

Exclusion Criteria:

1. Focal epilepsy
2. Paroxysmal nonepileptic seizures
3. Generalized/focal epilepsy mixed syndromes
4. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
5. Epileptic or developmental encephalopathy
6. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
7. Autism Spectrum Disorder
8. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
9. Seizures only during pregnancy
10. History of previous or current significant psychiatric disorder that would interfere with study requirements

Cohort 3: Longstanding IGE, Treatment Resistant

Inclusion Criteria:

1. Age ≥13 years at time of enrollment

2. Age ≥8 years at time of seizure onset

3. Clinical seizure(s) and history consistent with IGE. The only permitted seizure types are absence, myoclonus or generalized tonic-clonic convulsions

4. Occurrence of at least 1 seizure of any type in the 6 months prior to treatment onset

5. Patients must have had one of the following:

   1. GTCSs alone accompanied by generalized spike-wave consistent with IGE per adjudication review
   2. GTCSs with a history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review
   3. GTCSs associated with a history of absence and/or myoclonus, not accompanied by generalized spike-wave consistent with IGE per adjudication review
   4. A clear history of absence and/or myoclonus, accompanied by generalized spike-wave consistent with IGE per adjudication review

6. Availability of a complete medication history since initiation of treatment. This should include doses and date of initiation if possible, but minimum information would include name of drug, approximate duration of administration and reason for discontinuation, if applicable.

7. No competing cause of epilepsy (e.g. traumatic brain injury)

8. Treatment resistant IGE

   1. Initiation of treatment at least 2 years prior to enrollment
   2. Treatment resistance, as defined by failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination to achieve seizure freedom). ASMs taken at enrollment would count towards this minimum.
   3. Either or both of the following two:

   i. One GTCC per year over the last 2 years. ii. Any type of seizure at least every 3 months which can consist of either: disabling myoclonus or absence (in the opinion of the subject and investigator) or GTCC d. Such seizures were not primarily due to significant illness (e.g, URI is not significant unless temperature >101oF (38.3oC), nonadherence to antiseizure medications or >2 alcoholic beverages within 48 hrs of seizure e. Ongoing therapy with > 1 antiseizure medication

Exclusion Criteria:

1. Focal epilepsy
2. Paroxysmal nonepileptic seizures
3. Generalized/focal epilepsy mixed syndromes
4. Progressive neurological disorder (brain tumor, Alzheimer's disease, progressive myoclonic epilepsy, etc.)
5. Epileptic or developmental encephalopathy
6. Major medical co-morbidities (e.g. renal failure requiring dialysis, metastatic cancer, HIV, or significant liver or renal disease)
7. Autism Spectrum Disorder
8. History of chronic drug or alcohol abuse (misuse or excessive use that interferes with activities of daily living) within the last 2 years
9. Seizures only during pregnancy
10. History of previous or current significant psychiatric disorder that would interfere with study requirements
11. History of/suspicion of provoked seizures accounting for 25% or more of seizures over the prior 2 years (eg alcohol, non-adherence, significant sleep deprivation).

Trial design

320 participants in 3 patient groups

Cohort 1: Newly Diagnosed Idiopathic Generalized Epilepsy (IGE)

Description:

Cohort 1 will have IGE that was diagnosed within the prior year. We will follow these participants for a minimum of two years.

Cohort 2: Longstanding Treatment Responsive

Description:

Cohort 2 will consist of subjects with established IGE who have been responsive to treatment.

Cohort 3: Longstanding IGE, Treatment Resistant

Description:

Cohort 3 will consist of patients with established treatment-resistant IGE.