Subthalamic Nucleus Electrical Stimulation for Drug-resistant Focal Motor Epilepsy (STEM)

Subthalamic Nucleus Electrical Stimulation for Drug-resistant Focal Motor Epilepsy: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy, Drug Resistant
• Intervention / Treatment: Device: STN-DBS ON; Device: STN-DBS OFF

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.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liankun Ren, MD; Phone Number: +86 13681576621; Email: renlk2022@outlook.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Xuanwu Hospital, Beijing
      • Contact: Liankun Ren, MD; Phone Number: +86 13681576621; Email: renlk2022@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Stimulation; After randomization, participants will undergo STN-DBS ON in the 3-month blinded phase (Month 2 to Month 5) with the individual stimulation parameters determined in the parameter determination period, then continue to receive stimulation for the remainder of the study.	Device: STN-DBS ON; Stimulation ON
Sham Comparator: Sham Stimulation; After randomization, participants will undergo STN-DBS OFF in the 3-month blinded phase (Month 2 to Month 5) with 0mA current, then the stimulator will be turned on with individual stimulation parameters and left on for the remainder of the study.	Device: STN-DBS OFF; Stimulation OFF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Percent Change in Seizure Frequency	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.	Through the end of the three-month blinded phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure Responder Rate	The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.	Through the end of the three-month blinded phase
Seizure Severity	The percent change from baseline in seizure severity evaluated by Liverpool seizure severity scale (LSSS) across the double-blind period.	Through the end of the three-month blinded phase
Seizure-free Days	Change in percentage of seizure-free days over the entire blinded phase as compared to the entire baseline phase. The number of seizure-free days was normalized to 84-day baseline and blinded phases for each subject.	Through the end of the three-month blinded phase
The maximum length of seizure-free Intervals	Percentage change in the maximum length of seizure-free intervals over the entire blinded phase as compared to the entire baseline phase.	Through the end of the three-month blinded phase
Life quality evaluation	Percentage change from baseline in Quality of Life in Epilepsy-31 inventory (QOLIE-31) score at 3 months after randomization.	Through the end of the three-month blinded phase
Motor function evaluation	Percentage change from baseline in Unified Parkinson's Disease Rating Scale part II & part III (UPDRS II-III) score at 3 months after randomization.	Through the end of the three-month blinded phase
Cognitive function evaluation (MMSE)	Percentage change from baseline in Mini-Mental State Examination (MMSE) score at 3 months after randomization.	Through the end of the three-month blinded phase
Cognitive function evaluation (MoCA)	Percentage change from baseline in Montreal Cognitive Assessment (MoCA) score at 3 months after randomization.	Through the end of the three-month blinded phase
Psychologic Evaluation (Anxiety)	Percentage change from baseline in Hamilton Anxiety Rating Scale (HAMA) score at 3 months after randomization.	Through the end of the three-month blinded phase
Psychologic Evaluation (Depression)	Percentage change from baseline in Hamilton Depression Rating Scale (HAMD) score at 3 months after randomization.	Through the end of the three-month blinded phase
Sleep Quality	Percentage change from baseline in Pittsburgh Sleep Quality Index (PSQI) score at 3 months after randomization.	Through the end of the three-month blinded phase
Adverse Events	Rate of adverse events which were judged to be study-related throughout the study.	Through Month 11 of the open-label follow-up phase
Incidence of Sudden Unexpected Death in Epilepsy (SUDEP)	The number presented is for Definite and Probable SUDEP. The rate is calculated per 1000 subject years of follow-up.	Through Month 11 of the open-label follow-up phase

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Peking University; Beijing Tiantan Hospital; Qilu Hospital of Shandong University; Beijing Sanbo Brain Hospital
• Investigators: Principal Investigator: Liankun Ren, MD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 14, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2025
• Last Update Submitted That Met QC Criteria: July 12, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Subthalamic Nucleus; Focal Motor Epilepsy; Drug Resistant Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsies, Partial; Drug Resistant Epilepsy; Epilepsy; Epilepsy, Partial, Motor
• Other Study ID Numbers: 2023-174-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No