Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome

Обзор

The goal of this clinical trial is to explore a new type of personalized brain stimulation that works during day time and night time hours using the Medtronic Percept Deep Brain Stimulation (DBS) device in patients with Lennox-Gastaut Syndrome. The main question(s) this study aims to answer is: 1. Does using the personalized DBS reduce motor seizures compared to conventional DBS? 2. Is the number of seizures reported by caregivers different for patients using the personalized DBS? 3. How often do patients using the personalized DBS experience undesired side effects? Researchers will compare the personalized DBS that works night time, personalized DBS device that works during the day time, and conventional DBS. Participants will: 1. Have their seizures and sleep patterns recorded for 3-months 2. Assess their neurocognitive function 3. Answer questionnaires about communication, movement, and sleep quality 4. Wear a sleep headband and seizure warning watch for 5 nights 5. Complete a mood and sleep assessment 6. Have a 3T and possibly 7T MRI 7. Be implanted with stereo-encephalography and undergo 3\~5 days of monitoring 8. Have the stereo-encephalography taken out 9. Receive DBS implantation through surgery and have several months of stimulation and no stimulation periods 10. Have routine clinical visits to check on healing after surgery 11. Have their caregiver help them keep a dairy about their seizures, sleep and quality of life

Вмешательства

• Устройство Personalized Adaptive Deep Brain Stimulation Therapy
  This approach employs Bayesian optimized individualized stimulation parameters tailored to each patient. For 12 daytime hours (e.g., 8 AM-8 PM, adjustable per patient but fixed within each subject), the device will operate in continuous cycling mode delivering the optimized stimulation parameter (i.e patient specific frequency, pulse width, amplitude). The device will be programmed for AM and PM mode (e.g., 8AM-8 PM= AM mode; PM mode=8 PM-8 AM), the device will switched to adaptive mode manually
• Устройство Conventional Non-Personalized Deep Brain Stimulation Therapy
  The device will deliver conventional non-personalized stimulation parameters (145 Hz, 90 microsec, fixed current amplitude, 1 Min ON, 5 mins OFF) throughout both daytime and nighttime periods.

Первичные конечные точки

• Change in total tonic motor seizures between baseline (assessed by Caregiver reported seizures) and adaptive stimulation double-blinded study phase (assessed by Medtronic Percept PC system timeline data). [Срок оценки: Total tonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic seizure count at adaptive stimulation double-blinded study phase is for 4 months.]
• Change in total tonic motor seizures between baseline (assessed by Caregiver reported seizures) and adaptive stimulation double-blinded study phase (assessed by seizure detection watch data). [Срок оценки: Total tonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic seizure count at adaptive stimulation double-blinded study phase is for 4 months.]
• Change in total tonic-clonic motor seizures between baseline (assessed by Caregiver reported seizures) and adaptive stimulation double-blinded study phase (assessed by Medtronic Percept PC system timeline data). [Срок оценки: Total tonic-clonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic-clonic seizure count at adaptive stimulation double-blinded study phase is for 4 months.]
• Change in total tonic-clonic motor seizures between baseline (assessed by Caregiver reported seizures) and adaptive stimulation double-blinded study phase (assessed by seizure detection watch data). [Срок оценки: Total tonic-clonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic-clonic seizure count at adaptive stimulation double-blinded study phase is for 4 months.]
• Change in total tonic motor seizures between baseline (assessed by Caregiver reported seizures) and continuous stimulation double-blinded study phase (assessed by Medtronic Percept PC system timeline data). [Срок оценки: Total tonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic seizure count at continuous stimulation double-blinded study phase is for 4 months.]
• Change in total tonic motor seizures between baseline (assessed by Caregiver reported seizures) and continuous stimulation double-blinded study phase (assessed by seizure detection watch data). [Срок оценки: Total tonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic seizure count at continuous stimulation double-blinded study phase is for 4 months.]
• Change in total tonic-clonic motor seizures between baseline (assessed by Caregiver reported seizures) and continuous stimulation double-blinded study phase (assessed by Medtronic Percept PC system timeline data). [Срок оценки: Total tonic-clonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic-clonic seizure count at continuous stimulation double-blinded study phase is for 4 months.]
• Change in total tonic-clonic motor seizures between baseline (assessed by Caregiver reported seizures) and continuous stimulation double-blinded study phase (assessed by seizure detection watch data). [Срок оценки: Total tonic-clonic seizure count at baseline are for the 3 months prior to invasive EEG investigation. Total tonic-clonic seizure count at continuous stimulation double-blinded study phase is for 4 months.]
• Seizure Frequency as Reported by Caregivers' Diary [Срок оценки: From the start date of baseline measurement until the end date of the double-blinded phase of the study, assessed up to 33 months.]
• Frequency between participants with research-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6.0 [Срок оценки: From the date of device implantation until the end date of the double-blind study phase, assessed up to 25 months.]

Вторичные конечные точки (3)

• Participant sleep quality as assessed by Pittsburgh Sleep Quality Index questionnaire. [Срок оценки: From the start date of baseline measurement until the end date of the double-blinded phase of the study, assessed up to 33 months.]
• Participant quality of life as assessed by health-related, patient-centered Quality of Life in Neurological Disorders (Neuro-Qol) questionnaire [Срок оценки: From the start date of baseline measurement until the end date of the double-blinded phase of the study, assessed up to 33 months.]
• Participant quality of life as assessed by Patient-Reported Outcomes Measurement Information System-Profile 57 (PROMIS-57) version 2.1 [Срок оценки: From the start date of baseline measurement until the end date of the double-blinded phase of the study, assessed up to 33 months.]

Критерии участия

Критерии включения

• 18-65 years of age
• Diagnosis of Lennox-Gastaut Syndrome (LGS) with confirmed generalized seizures, including generalized tonic or tonic-clonic (GTC) seizures. Participants may also have complex partial, atypical absences or atonic seizures, but these will not count toward minimum seizure frequency eligibility.
• Diagnosis is based on prior video EEG confirmation performed in the last 3 years. Scalp EEG showing slow spike-wave discharges and paroxysmal fast activity.
• At least four seizures per month (GTC or tonic) on average during the three months preceding enrollment.
• Medically intractable epilepsy, defined as failure to achieve acceptable seizure control despite trials of at least two antiseizure medications (ASMs).
• Nonlocalized seizures, as determined by standard diagnostic studies.
• Stable doses of two or more ASMs for at least one month prior to enrollment (rescue benzodiazepines for acute seizure clusters permitted).
• Participants with vagus nerve stimulation (VNS) must have stable settings for at least two months prior to enrollment and throughout the study.
• Subjective reporting of sleep disturbances.
• Participant or legal guardian can provide informed consent and maintain an online seizure log, alone or with assistance.
• Participant is willing to remain on a stable ASM regimen (except use of variable dose of rescue medications permitted) throughout the study and able to attend scheduled clinic visits.
• Reliable caregiver is available to assist with seizure diary maintenance.

Критерии исключения

• Predominant seizure type is focal-onset seizures.
• Anatomical brain abnormalities precluding DBS implantation, or discrete brain lesions on MRI (e.g., cortical malformation, tuber, or sclerosis).
• Unable to obtain brain MRI due to metal that is not compatible with 3T MRI.
• History of psychogenic non-epileptic seizures or unstable psychiatric disorders, including suicidal ideation or intent within the last six months.
• Clinically significant medical conditions increasing risk for pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension).
• Participant is pregnant or plans to become pregnant during the study.
• Participation in another therapeutic investigational drug or device study.
• Requirement for diathermy treatments during physical or occupational therapy.
• In the opinion of the investigator or eligibility adjudication committee, the subject is unsuitable for the procedure.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07568860 · STUDY00027660

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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