cTBS Targeting Cerebellum for Drug-refractory Epilepsy

Study Overview
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Brief Summary
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This study aims to observe the effect and safety of cerebellar continuous θ burst stimulation (cTBS) for drug-refractory epilepsy(DRE), in order to provide a new treatment for DRE and improve the quality of life of those patients. A total of 44 patients with DRE will have cTBS via accurate navigation to bilateral cerebellar dentate nuclei. Patients will be randomised into 2 groups in a crossover trial design to have 2 week periods of cTBS separated by 8 week washout periods, following which the patient will cross over to have the opposite condition for a further 2 week. Frequency and symptoms of seizures, scalp EEG, clinical scores, and QOLIE-31 were assessed at baseline and after 1 and 2 month of treatment.

Official Title
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Bilateral Continuous Theta Burst Stimulation of Cerebellum for Drug-refractory Epilepsy: A Double Blind, Randomised, Single Centre, Crossover Clinical Trial

Conditions
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Drug Refractory Epilepsy

Intervention / Treatment
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* Device: cTBS First
* Device: Pseudo-stimulation First


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a) Participants who are in line with the diagnostic criteria for epilepsy, b) Participants who are diagnosed as drug-refractory epilepsy, c) Participants who has duration of epilepsy ≥2 years and seizure frequency ≥2 times per month, d) The type and dosage of anti-epileptic drugs do not change during the experiment, e) Participants or their families reject invasive therapy, such as operation, f) Participants and their families are aware of this study and sign informed consent. Exclusion Criteria: a) Participants who are in status epilepticus, b) Participants who are complicated with serious infection, cerebrovascular disease, malignant tumor and other nervous system diseases, with serious dysfunction of heart, liver, kidney and other organs, and with psychiatric disorders, c) Participants who are diagnosed as syncope, hysteria or other non-epileptic attacks, d) Participants who are in pregnancy or lactating, e) Participants who have incomplete clinical data, f) Patients have contraindications of repeated transcranial magnetic stimulation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cTBS First<br>The first stage, participants received cTBS treatment for a total of 10 times during two weeks, then followed up for eight weeks; the second stage, participants are treated with pseudo-stimulation for a total of 10 times during two weeks, then followed up for 8 weeks similarly. | Device: cTBS First<br>* Continuous θ-burst stimulation (cTBS) is characterized by plexus stimulation. The stimulation intensity was 80% resting motor threshold (RMT) at 50Hz of intra plexus pulse while the frequency of inter plexus pulse is 5Hz, the duration was 33.2s, and the number of stimulation pulses was 600. Two groups of stimulation were repeated in each cerebellar dentate nucleus with an interval of 5 min in each group.<br>|
| Experimental: Pseudo-stimulation First<br>The first stage, participants received pseudo-stimulation treatment for a total of 10 times during two weeks, then followed up for eight weeks; the second stage, participants are treated with cTBS for a total of 10 times during two weeks, then followed up for 8 weeks similarly. | Device: Pseudo-stimulation First<br>* The transcranial magnetic stimulator operating system has a built-in control group option, in which the stimulation parameters are set consistent with the research group, which can realize the operation of only sound without stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seizure reduction rate in pre- and post-treatment | A 28-day baseline for seizure frequency will be recorded by the patients themselves or their relatives before therapy and then compare to the frequency at 4-week and 8-week after treatment, finally, the rate of reduction in seizure frequency was obtained | 8 weeks | 
| responder rate | proportion of people with a 50% or greater reduction in seizure frequency following the treatment period | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QOLIE-31 scale scores | Quality of Life in Epilepsy-31. Scores range from 0 to 100, with higher scores indicating better quality of life. | 8 weeks | 
| scalp electroencephalogram | Routine scalp electroencephalogram at 40 min | 8 weeks | 
| IQ | Wechsler Abbreviated Scale of Intelligence. Above 130 points very excellent, 120-129 excellent, 110-119 above average, 90-109 average, 80-89 below average, 70-79 critical level, below 69 mental retardation, 50-69 mild mental retardation, 35-49 moderate mental retardation, 20-34 severe mental retardation, less than 20 extremely severe mental retardation. | 8 weeks | 
| MQ | Wechsler Memory Scale. Above 130 points very excellent, 120-129 excellent, 110-119 above average, 90-109 average, 80-89 below average, 70-79 critical level, below 69 mental retardation, 50-69 mild mental retardation, 35-49 moderate mental retardation, 20-34 severe mental retardation, less than 20 extremely severe mental retardation. | 8 weeks | 
| MoCA | Montreal Cognitive Assessment. A max score is 30 points, and a score ≥ 26 is considered normal. | 8 weeks | 
| MMSE | Mini-Mental State Examination. The normal values are defined as: illiterates >17, primary school >20, junior high school or above >24. | 8 weeks | 
| HAMD | Hamilton Depression Scale. Total score <7 means normal; between 7 and 17 means possible depression; between 17 and 24 , definitely have depression; >24 means severe depression. | 8 weeks | 
| HAMA | Hamilton Anxiety Scale. The total score ≥29 may be severe anxiety; ≥21, obvious anxiety; ≥14, definite anxiety; ≥7, may have anxiety; If the score <7, there are no symptoms of anxiety. | 8 weeks | 
| SCL-90 | Self-reporting Inventory. The total symptom index scores ranged from 1 to 1.5, indicating that the subjects did not feel the symptoms listed in the scale. Between 1.5 and 2.5, indicates that the subject feels a little symptomatic, but not occur frequently. Between 2.5 and 3.5, indicates that the subject feels symptoms, and is mild to moderate. The score between 3.5 and 4.5 indicates that the subjects feel symptoms, and the degree was moderate to severe. A score between 4.5 and 5 indicates that the subject feels symptoms, and the frequency and intensity are very severe. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Refractory Epilepsy, Continuous θ Burst Stimulation, Cerebellar Dentate Nucleus