Clinical trial NCT06248333: Subthalamic Nucleus Electrical Stimulation for Drug-resistant Focal Motor Epilepsy
Official title: Subthalamic Nucleus Electrical Stimulation for Drug-resistant Focal Motor Epilepsy: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Epilepsy, Drug Resistant
Keywords: Deep Brain Stimulation
Drug Resistant Epilepsy
Subthalamic Nucleus
Focal Motor Epilepsy
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Beijing Tiantan Hospital
name: Beijing Sanbo Brain Hospital
name: Qilu Hospital of Shandong University
name: Peking University
First posted: 2024-02-08
Enrollment: 33
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After completion of DBS surgery (Month 0), participants will undergo an 8-day parameter exploration period after 1-month postoperative recovery (month 1), and DBS off after individual parameters have been determined. At Month 2, participants will be randomly assigned to one of two groups: Group A or Group B. Group A (Activate Stimulation) will have their stimulator turned on after randomization. Group B (Sham Stimulation) will receive sham stimulation, meaning the stimulator will remain off until Study Month 5. At Month 5, Group A will continue to receive stimulation and not have the stimulator turned off, and the stimulator in Group B will be turned on and left on for the remainder of the study (Month 11).
Primary purpose: TREATMENT

Brief summary: The primary objective of this research is to study the efficacy and safety of deep brain stimulation (DBS) of subthalamic nucleus (STN) as adjunctive therapy for reducing the frequency of seizures in drug-resistant focal motor epilepsy.

Detailed description: This is a multicenter, randomized, double-blind, sham-controlled, parallel-group trial that aims to investigate the efficacy of STN-DBS in reducing the frequency of seizures in drug-resistant focal motor epilepsy. Participants who were eligible for the inclusion criteria and ineligible for the exclusion criteria will be randomly assigned into two groups by a 1:1 ratio. The primary purpose of this study is to compare active STN-DBS with sham STN-DBS in reducing seizure frequency. Both intent analysis (ITT) and compliance program set (PPS) were used for analysis. Only high-volume centers with a proven track record will be included. The STEM trial will be conducted in 5 sites in China.

Eligibility criteria: Inclusion Criteria:

* 14-65 years of age, inclusive, at Screening Visit.
* Refractory to anti-seizure medications (ASMs).
* Diagnosed with focal motor epilepsy, which meets the following items:

  1. Seizure mainly presents as focal tonic, myoclonic, or primary motor seizure (including primary sensory seizure), with or without secondary bilateral tonic-clonic seizure.
  2. After a comprehensive evaluation, the epileptogenic zone was presumed to predominantly involve the unilateral or bilateral central area (precentral gyrus, postcentral gyrus, and paracentral lobule) or supplementary motor area according to comprehensive presurgical evaluation.
* Within 1 month prior to the Screening Visit (M-3), the following conditions are met:

  1. At least 3 focal onset seizures (with or without secondary bilateral tonic-clonic seizure).
  2. Subject is receiving at least one type of ASM\[s\], and the regimen has been stable (no addition or removal of ASM\[s\] \[not counting brief rescue medicines such as benzodiazepines\]; dose adjustments are permitted to ASM\[s\]).
* Within the baseline period (3 months after the Screening Visit \[M-3\]), the following conditions are met:

  1. The patient or their caregiver is capable of completing the seizure diary.
  2. Seizure diary shows an average of 3 or more partial-onset seizures (with or without secondary bilateral tonic-clonic seizure) per month during the Baseline Period, with no more than 30 days between seizures.
  3. The regimen of ASM\[s\] has been stable (no addition or removal of ASM\[s\] \[not counting brief rescue medicines such as benzodiazepines\]; dose adjustments are permitted to ASM\[s\]).
* After comprehensive preoperative evaluation, patients who are considered unsuitable for or refuse resection surgery, or those for whom the effects of epileptic focus resection and thermocoagulation surgery are not satisfactory.
* Informed consent signed.

Exclusion Criteria:

* Diagnosed with generalized or hereditary epilepsy with ion channel gene mutations;
* Seizures mainly present as complex motor seizures (e.g., hyperkinetic, automatisms, etc.);
* Tonic-clonic status epilepticus within12 months;
* Psychogenic non-epileptic seizures within 12 months;
* Structural lesion of the subthalamic nucleus;
* Presence of implanted electrical stimulation medical device anywhere in the body (e.g., pacemaker, spinal cord stimulator, responsive neurostimulation) or any metallic implants in the head (e.g., aneurysm clips, cochlear implants). Note: Vagal nerve stimulators are allowed if the parameter remains stable for at least 3 months prior to the screening visit;
* Risk factors that would put the participant at risk for intraoperative or postoperative bleeding. (e.g., coagulation abnormalities, etc.) or the need for chronic anticoagulation or antiplatelet aggregation medications;
* IQ \< 55 or severe cognitive dysfunction, unable to complete the study;
* Diagnosed with a progressive neurological disorder (including progressive Rasmussen's encephalitis, etc.);
* Diagnosed with a severe neuropsychiatric disorder such as dementia, major depression (admission to a psychiatric specialty/hospital within 5 years or any suicidal or self-injurious tendencies), schizophrenia, or neurodegenerative disorders;
* Diagnosed with other serious physical disorders, internal diseases or severe abnormalities in liver or kidney function;
* Pregnant, or planning to pregnant within 2 years;
* Participation in another clinical study within 3 months;
* Not suitable for enrollment as assessed by the multidisciplinary team of the center.

Primary outcomes:
measure: Median Percent Change in Seizure Frequency
timeFrame: Through the end of the three-month blinded phase
Secondary outcomes:
measure: Seizure Responder Rate
timeFrame: Through the end of the three-month blinded phase
measure: Seizure Severity
timeFrame: Through the end of the three-month blinded phase
measure: Seizure-free Days
timeFrame: Through the end of the three-month blinded phase
measure: The maximum length of seizure-free Intervals
timeFrame: Through the end of the three-month blinded phase
measure: Life quality evaluation
timeFrame: Through the end of the three-month blinded phase
measure: Motor function evaluation
timeFrame: Through the end of the three-month blinded phase
measure: Cognitive function evaluation (MMSE)
timeFrame: Through the end of the three-month blinded phase
measure: Cognitive function evaluation (MoCA)
timeFrame: Through the end of the three-month blinded phase
measure: Psychologic Evaluation (Anxiety)
timeFrame: Through the end of the three-month blinded phase
measure: Psychologic Evaluation (Depression)
timeFrame: Through the end of the three-month blinded phase
measure: Sleep Quality
timeFrame: Through the end of the three-month blinded phase
measure: Adverse Events
timeFrame: Through Month 11 of the open-label follow-up phase
measure: Incidence of Sudden Unexpected Death in Epilepsy (SUDEP)
timeFrame: Through Month 11 of the open-label follow-up phase
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Beijing
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Liankun Ren, MD
role: PRINCIPAL_INVESTIGATOR
References: