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

Overview

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.

Interventions

• Device STN-DBS ON
  Stimulation ON
• Device STN-DBS OFF
  Stimulation OFF

Primary outcome measures

• Median Percent Change in Seizure Frequency [Time frame: Through the end of the three-month blinded phase]

Secondary outcome measures (12)

• Seizure Responder Rate [Time frame: Through the end of the three-month blinded phase]
• Seizure Severity [Time frame: Through the end of the three-month blinded phase]
• Seizure-free Days [Time frame: Through the end of the three-month blinded phase]
• The maximum length of seizure-free Intervals [Time frame: Through the end of the three-month blinded phase]
• Life quality evaluation [Time frame: Through the end of the three-month blinded phase]
• Motor function evaluation [Time frame: Through the end of the three-month blinded phase]
• Cognitive function evaluation (MMSE) [Time frame: Through the end of the three-month blinded phase]
• Cognitive function evaluation (MoCA) [Time frame: Through the end of the three-month blinded phase]
• Psychologic Evaluation (Anxiety) [Time frame: Through the end of the three-month blinded phase]
• Psychologic Evaluation (Depression) [Time frame: Through the end of the three-month blinded phase]
• Sleep Quality [Time frame: Through the end of the three-month blinded phase]
• Adverse Events [Time frame: Through Month 11 of the open-label follow-up phase]

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:

• 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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Xuanwu Hospital, Beijing — Beijing

Identifiers

NCT: NCT06248333 · 2023-174-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗