Clinical trial NCT05374928: Human Epilepsy Project 3
Official title: Human Epilepsy Project 3: Newly Diagnosed Idiopathic Generalized Epilepsy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Idiopathic Generalized Epilepsy
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2022-05-16
Enrollment: 320
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed IGE, as well as a cohort of subjects with established IGE.

Brief summary: 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.


Eligibility 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).

Primary outcomes:
measure: Number of Individual Seizures
timeFrame: Baseline
measure: Number of Cluster Seizures
timeFrame: Baseline
measure: Number of episodes of non-adherence
timeFrame: Baseline
measure: Average daily steps
timeFrame: Baseline
measure: Average distance walked
timeFrame: Baseline
measure: Average heart rate
timeFrame: Baseline
measure: Average daily sleep duration
timeFrame: Baseline
measure: Average daily wake duration
timeFrame: Baseline
measure: Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score
timeFrame: Baseline, Month 12
measure: Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score
timeFrame: Baseline, Month 24
measure: Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score
timeFrame: Month 12, Month 24
measure: Change in General Anxiety Disorder-7 Screener (GAD-7) Score
timeFrame: Baseline, Month 12
measure: Change in General Anxiety Disorder-7 Screener (GAD-7) Score
timeFrame: Baseline, Month 24
measure: Change in General Anxiety Disorder-7 Screener (GAD-7) Score
timeFrame: Month 12, Month 24
measure: Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline
measure: Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Month 12
measure: Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Month 24
measure: Cogstate Neuropsychological Assessment Score
timeFrame: Baseline
measure: Cogstate Neuropsychological Assessment Score
timeFrame: Month 12
measure: Cogstate Neuropsychological Assessment Score
timeFrame: Month 24
measure: Wide Range Achievement Test (WRAT-4) Score
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy Sleep Center
state: Maryland
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: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health - Comprehensive Epilepsy Center (CEC)
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Melbourne
country: Australia
facility: Monash University
state: Clayton VIC
Study officials:
References: