Subthalamic Nucleus Electrical Stimulation for Drug-resistant Focal Motor Epilepsy: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Median Percent Change in Seizure Frequency
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
One day before the first programming, the grouper and the programmer will release the cover independently. Only the grouper and the programmer will know the group information of each patient, in which the programmer does not communicate with the patient about the programming parameters. After each programming, the results are uniformly placed in the programmer to keep the others (patients, neurologists) blind about grouping and parameters. The evaluation will be finished by neurologists, who do not participate in the surgical treatment and programmer. So that the participants, care providers, investigators, and outcomes assessors will not know which group are assigned to from randomization (Month 2) to Month 5. The statistical team is independent of other researchers.
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Seizure mainly presents as focal tonic, myoclonic, or primary motor seizure (including primary sensory seizure), with or without secondary bilateral tonic-clonic seizure.
- •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:
- •At least 3 focal onset seizures (with or without secondary bilateral tonic-clonic seizure).
- •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:
- •The patient or their caregiver is capable of completing the seizure diary.
- •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.
- •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.
排除标准
- •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.
结局指标
主要结局
Median Percent Change in Seizure Frequency
时间窗: Through the end of the three-month blinded phase
Seizure frequency (SF28) is defined as seizure count per month (28-day) period. The SF28 is calculated as follows, where D=total number of days for which seizure information is collected for the specific 28-day interval: SF28=(Total number of seizures in D days/D)\*28. In addition, the baseline seizure frequency is defined as mean of 3-month SF28 in the baseline period. The seizure frequency in double-blind phase is defined as SF28 per month during the double-blind period. Percent change in seizure frequency=100\*(double-blind SF28-baseline SF28)/baseline SF28.
次要结局
- Psychologic Evaluation (Anxiety)(Through the end of the three-month blinded phase)
- Psychologic Evaluation (Depression)(Through the end of the three-month blinded phase)
- Adverse Events(Through Month 11 of the open-label follow-up phase)
- Seizure-free Days(Through the end of the three-month blinded phase)
- Cognitive function evaluation (MMSE)(Through the end of the three-month blinded phase)
- Sleep Quality(Through the end of the three-month blinded phase)
- The maximum length of seizure-free Intervals(Through the end of the three-month blinded phase)
- Cognitive function evaluation (MoCA)(Through the end of the three-month blinded phase)
- Incidence of Sudden Unexpected Death in Epilepsy (SUDEP)(Through Month 11 of the open-label follow-up phase)
- Seizure Responder Rate(Through the end of the three-month blinded phase)
- Seizure Severity(Through the end of the three-month blinded phase)
- Life quality evaluation(Through the end of the three-month blinded phase)
- Motor function evaluation(Through the end of the three-month blinded phase)
研究者
Liankun_Ren
Professor
Xuanwu Hospital, Beijing