Human Epilepsy Project 3

Idiopathic Generalized Epilepsy Clinical Trial

— HEP3  

Official title:

Human Epilepsy Project 3: Newly Diagnosed Idiopathic Generalized Epilepsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05374928
• Other study ID #: 19-01030
• Status: Recruiting
• Start date: March 9, 2020
• Est. completion date: June 2025

Study information

• Verified date: January 2024
• Source: NYU Langone Health
• Contact: Jacqueline French, MD
• Phone: 646-558-0839
• Email: Jacqueline.French[@]nyulangone.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Epilepsy
• Epilepsy, Generalized
• Idiopathic Generalized Epilepsy

Locations

Country	Name	City	State
Australia	Monash University	Melbourne	Clayton VIC
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Mid-Atlantic Epilepsy Sleep Center	Bethesda	Maryland
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Mount Sinai Hospital	New York	New York
United States	Northwell Health	New York	New York
United States	NYU Langone Health - Comprehensive Epilepsy Center (CEC)	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	Minnesota Epilepsy Group	Saint Paul	Minnesota
United States	University of Utah Hospital	Salt Lake City	Utah
United States	University of Texas Health Science Center	San Antonio	Texas
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Individual Seizures	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Primary	Number of Cluster Seizures	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Primary	Number of episodes of non-adherence	Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)	Baseline
Primary	Average daily steps	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Primary	Average distance walked	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Primary	Average heart rate	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study.	Baseline
Primary	Average daily sleep duration	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study. Using the Embleema Patient Web App, participants will be able to consult their activity and sleep data in interactive graphs.	Baseline
Primary	Average daily wake duration	Participants will be provided a Fitbit Inspire HR watch and will be trained to open an account on fitbit.com and synchronize their Fitbit watch data into their Fitbit cloud account. Daily steps is synchronized and collected for this study. Using the Embleema Patient Web App, participants will be able to consult their activity and sleep data in interactive graphs.	Baseline
Primary	Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Baseline, Month 12
Primary	Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Baseline, Month 24
Primary	Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score	QOLIE-10 assesses the patient's quality of life. There are 11 total items. The total score range is 10-51; with higher scores indicating greater impairment. The total score is the sum of scores for all questions divided by the number of items answered. Thus, if a patient skipped an item, it is not reflected in the total score.	Month 12, Month 24
Primary	Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Baseline, Month 12
Primary	Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Baseline, Month 24
Primary	Change in General Anxiety Disorder-7 Screener (GAD-7) Score	This will only be reported for adults. GAD-7 consists of 7 problems. Participants report how often they have been bothered by the 7 problems over the last 2 weeks on a Likert Scale from 0 (not at all) to 3 (nearly every day). The total score range is 0-21; the higher the score, the more severe the anxiety. 0-4=minimal anxiety, 5-9=mild, 10-14=moderate, 15-21=severe anxiety.	Month 12, Month 24
Primary	Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Baseline
Primary	Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Month 12
Primary	Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) - 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention	Month 24
Primary	Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Baseline
Primary	Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Month 12
Primary	Cogstate Neuropsychological Assessment Score	The Cogstate is a battery of online computerized tests that assesses functions such as attention, memory, and processing speed. Scores are normalized to the range of 0-100th percentile based on speed of test completion and task accuracy. A higher percentile score indicates higher levels of cognitive functioning within the tested domain as compared to controls.	Month 24
Primary	Wide Range Achievement Test (WRAT-4) Score	WRAT4 is an academic skills assessment which measures reading skills, math skills, spelling, and comprehension. Only the Word Reading portion of the assessment will be administered. The total raw score range is from 0-70, with a normalized score range of 55-145. The higher the score, the more advanced the participant's reading comprehension skills for their age range.	Baseline