NCT07568860 - Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

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).

Caregiver reported seizures will provide baseline total tonic motor seizure count. Medtronic Percept PC system timeline data will provide adaptive stimulation double-blinded study phase total tonic motor seizure count. The total tonic motor seizure counts between baseline and the adaptive stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

Time frame: 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).

Caregiver reported seizures will provide baseline total tonic motor seizure count. Seizure detection watch data will provide adaptive stimulation double-blinded study phase total tonic motor seizure count. The total tonic motor seizure counts between baseline and the adaptive stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

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).

Caregiver reported seizures will provide baseline total tonic-clonic motor seizure count. Medtronic Percept PC system timeline data will provide adaptive stimulation double-blinded study phase total tonic-clonic motor seizure count. The total tonic-clonic motor seizure counts between baseline and the adaptive stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

Time frame: 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).

Caregiver reported seizures will provide baseline total tonic-clonic motor seizure count. Seizure detection watch data will provide adaptive stimulation double-blinded study phase total tonic-clonic motor seizure count. The total tonic-clonic motor seizure counts between baseline and the adaptive stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

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).

Caregiver reported seizures will provide baseline total tonic motor seizure count. Medtronic Percept PC system timeline data will provide continuous stimulation double-blinded study phase total tonic motor seizure count. The total tonic motor seizure counts between baseline and the continuous stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

Time frame: 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).

Caregiver reported seizures will provide baseline total tonic motor seizure count. Seizure detection watch data will provide continuous stimulation double-blinded study phase total tonic motor seizure count. The total tonic motor seizure counts between baseline and the continuous stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

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).

Caregiver reported seizures will provide baseline total tonic-clonic motor seizure count. Medtronic Percept PC system timeline data will provide continuous stimulation double-blinded study phase total tonic-clonic motor seizure count. The total tonic-clonic motor seizure counts between baseline and the continuous stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

Time frame: 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).

Caregiver reported seizures will provide baseline total tonic-clonic motor seizure count. Seizure detection watch data will provide continuous stimulation double-blinded study phase total tonic-clonic motor seizure count. The total tonic-clonic motor seizure counts between baseline and the continuous stimulation double-blinded study phase will be compared to see if there was a reduction from baseline.

Seizure Frequency as Reported by Caregivers' Diary

Caregivers will be contacted biweekly by the study coordinator to minimize missed events and ensure accurate reporting. The frequency of seizures reported by caregivers will serve as the primary metric for statistical analysis.

Time frame: 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

Frequency between participants with research-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6.0. This is a qualitative collection of information via participant report or clinical observation, but will be input as quantitative (e.g., a headache can be classified as "1-Mild, 2-Moderate, and 3-Severe").

Time frame: From the date of device implantation until the end date of the double-blind study phase, assessed up to 25 months.

Frequency within participants with research-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6.0

Frequency within participants with research-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v6.0. This is a qualitative collection of information via participant report or clinical observation, but will be input as quantitative (e.g., a headache can be classified as "1-Mild, 2-Moderate, and 3-Severe").

Time frame: From the date of device implantation until the end date of the double-blind study phase, assessed up to 25 months.

Secondary Outcomes

Participant sleep quality as assessed by Pittsburgh Sleep Quality Index questionnaire.

The minimum score is 0 and the maximum score is 21, with lower scores meaning better sleep quality.

Time frame: 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

Participant quality of life will be assessed by five Neuro-Qol questionnaire domains, with raw scores from each domain converted into a T-score. Anxiety, Fatigue, Depression, Cognitive Function, Emotional and Behavioral Dyscontrol. A T-score of 50 represents the reference population mean, with a T-score of 60 being one standard deviation (SD) above the mean and a T-score of 40 being one SD below the mean. A higher T-score in the domains of Anxiety, Fatigue, Depression, Emotional and Behavioral Dyscontrol means worse outcomes than the reference population. A higher T-score in the Cognitive Function means better outcomes than the reference population.

Time frame: 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

PROMIS-57 measures quality of life across seven domains, with raw scores from each domain converted into a T-score. A T-score of 50 represents the reference population mean, with a T-score of 60 being one standard deviation (SD) above the mean and a T-score of 40 being one SD below the mean. A higher T-score in the domains of fatigue, anxiety, pain interference, pain intensity, and sleep disturbance means worse outcomes than the reference population. A higher T-score in the domains of physical function and ability to participate in social roles and activities means better outcomes than the reference population.

Time frame: From the start date of baseline measurement until the end date of the double-blinded phase of the study, assessed up to 33 months.

Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts