Human Epilepsy Project 3 (HEP3)

• ClinicalTrials.gov Identifier: NCT05374928
• Recruitment Status: Recruiting
• First Posted: May 16, 2022
• Last Update Posted: May 16, 2022
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Study Description

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.

Condition or disease
Idiopathic Generalized Epilepsy

Study Design

• Study Type: Observational
• Estimated Enrollment: 325 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Human Epilepsy Project 3: Newly Diagnosed Idiopathic Generalized Epilepsy
• Actual Study Start Date: March 9, 2020
• Estimated Primary Completion Date: March 2024
• Estimated Study Completion Date: March 2025

Groups and Cohorts

Group/Cohort
Cohort 1: Newly Diagnosed Idiopathic Generalized Epilepsy (IGE); 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; Cohort 2 will consist of subjects with established IGE who have been responsive to treatment.
Cohort 3: Longstanding IGE, Treatment Resistant; Cohort 3 will consist of patients with established treatment-resistant IGE.

Outcome Measures

Primary Outcome Measures :

1. Number of Individual Seizures [ Time Frame: Baseline ]
   Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)
2. Number of Cluster Seizures [ Time Frame: Baseline ]
   Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)
3. Number of episodes of non-adherence [ Time Frame: Baseline ]
   Self-reported via the Seer Seizure Diary App (https://app.seermedical.com)
4. Average daily steps [ Time Frame: Baseline ]
   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.
5. Average distance walked [ Time Frame: Baseline ]
   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.
6. Average heart rate [ Time Frame: Baseline ]
   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.
7. Average daily sleep duration [ Time Frame: Baseline ]
   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.
8. Average daily wake duration [ Time Frame: Baseline ]
   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.
9. Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score [ Time Frame: Baseline, Month 12 ]
   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.
10. Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score [ Time Frame: Baseline, Month 24 ]
    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.
11. Change in Quality of Life in Epilepsy Inventory-10 (QOLIE-10) Score [ Time Frame: Month 12, Month 24 ]
    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.
12. Change in General Anxiety Disorder-7 Screener (GAD-7) Score [ Time Frame: Baseline, Month 12 ]
    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.
13. Change in General Anxiety Disorder-7 Screener (GAD-7) Score [ Time Frame: Baseline, Month 24 ]
    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.
14. Change in General Anxiety Disorder-7 Screener (GAD-7) Score [ Time Frame: Month 12, Month 24 ]
    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.
15. Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline ]
    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
16. Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Month 12 ]
    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
17. Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Month 24 ]
    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
18. Cogstate Neuropsychological Assessment Score [ Time Frame: Baseline ]
    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.
19. Cogstate Neuropsychological Assessment Score [ Time Frame: Month 12 ]
    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.
20. Cogstate Neuropsychological Assessment Score [ Time Frame: Month 24 ]
    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.
21. Wide Range Achievement Test (WRAT-4) Score [ Time Frame: Baseline ]
    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.

Biospecimen Retention:   Samples With DNA

Participants will be asked to provide urine for small molecule analysis, blood if he/she is 13-17 years old, or protein, cell-free DNA, metabolomics, and RNA analyses, and a stool sample for microbiome analysis.

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients with newly diagnosed IGE, as well as a cohort of subjects with established IGE.

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).

Contacts and Locations

Contacts

Contact: Jacqueline French, MD; 646-558-0839; Jacqueline.French@nyulangone.org

Contact: Orrin Devinsky, MD; 646-558-0803; Orrin.Devinsky@nyulangone.org

Locations

United States, California

University of California San Francisco (UCSF); Recruiting

San Francisco, California, United States, 94143

United States, Connecticut

Yale University; Recruiting

New Haven, Connecticut, United States, 06520

United States, District of Columbia

Georgetown University; Recruiting

Washington, District of Columbia, United States, 20057

United States, Florida

University of Miami; Recruiting

Miami, Florida, United States, 33146

United States, Maine

Maine Medical Center; Recruiting

Portland, Maine, United States, 04102

United States, Maryland

The Johns Hopkins Hospital; Not yet recruiting

Baltimore, Maryland, United States, 21287

Mid-Atlantic Epilepsy Sleep Center; Recruiting

Bethesda, Maryland, United States, 20817

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Minnesota Epilepsy Group; Recruiting

Saint Paul, Minnesota, United States, 55113

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63130

United States, New Jersey

St. Barnabas Medical Center; Recruiting

Livingston, New Jersey, United States, 07039

United States, New York

NYU Langone Health - Comprehensive Epilepsy Center (CEC); Recruiting

New York, New York, United States, 10016

Principal Investigator: Orrin Devinsky, MD

Sub-Investigator: Jacqueline French, MD

Mount Sinai Hospital; Not yet recruiting

New York, New York, United States, 10029

Northwell Health; Recruiting

New York, New York, United States, 10065

United States, Pennsylvania

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

University of Texas Health Science Center; Recruiting

San Antonio, Texas, United States, 77030

United States, Utah

University of Utah Hospital; Not yet recruiting

Salt Lake City, Utah, United States, 84132

Australia, Clayton VIC

Monash University; Recruiting

Melbourne, Clayton VIC, Australia, 3800

Sponsors and Collaborators

NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT05374928
• Other Study ID Numbers: 19-01030
• First Posted: May 16, 2022
• Last Update Posted: May 16, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
• Supporting Materials: Study Protocol
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: Researchers who provide a methodologically sound proposal will have access to the data upon reasonable request. All requests for study data will be submitted using a standardized form that will be available on the HEP3 website (www.humanepilepsyproject.org).

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Epilepsy; Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases