cTBS Targeting Cerebellum for Drug-refractory Epilepsy

Drug Refractory Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05042726
• Other study ID #: XijingSN
• Status: Completed
• Phase: N/A
• Start date: August 2, 2021
• Est. completion date: August 26, 2022

Study information

• Verified date: August 2022
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: August 26, 2022
• Est. primary completion date: August 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Refractory Epilepsy
• Drug Resistant Epilepsy
• Epilepsy

Intervention

Device:
• cTBS First
Continuous ?-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.
• Pseudo-stimulation First
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.

Locations

Country	Name	City	State
China	Xijing Hospital	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Brighina F, Daniele O, Piazza A, Giglia G, Fierro B. Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports. Neurosci Lett. 2006 Apr 24;397(3):229-33. doi: 10.1016/j.neulet.2005.12.050. Epub 2006 Jan 19. — View Citation

Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3. — View Citation

Cooper YA, Pianka ST, Alotaibi NM, Babayan D, Salavati B, Weil AG, Ibrahim GM, Wang AC, Fallah A. Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence. Epilepsia Open. 2017 Dec 27;3(1):55-65. doi: 10.1002/epi4.12092. eCollection 2018 Mar. — View Citation

Forsgren L, Beghi E, Oun A, Sillanpaa M. The epidemiology of epilepsy in Europe - a systematic review. Eur J Neurol. 2005 Apr;12(4):245-53. doi: 10.1111/j.1468-1331.2004.00992.x. — View Citation

George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology. 2010 Jan;35(1):301-16. doi: 10.1038/npp.2009.87. — View Citation

Hsu WY, Cheng CH, Lin MW, Shih YH, Liao KK, Lin YY. Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis. Epilepsy Res. 2011 Oct;96(3):231-40. doi: 10.1016/j.eplepsyres.2011.06.002. Epub 2011 Jun 29. — View Citation

Koc G, Gokcil Z, Bek S, Kasikci T, Eroglu E, Odabasi Z. Effects of continuous theta burst transcranial magnetic stimulation on cortical excitability in patients with idiopathic generalized epilepsy. Epilepsy Behav. 2017 Dec;77:26-29. doi: 10.1016/j.yebeh.2017.09.011. Epub 2017 Oct 23. — View Citation

Krook-Magnuson E, Szabo GG, Armstrong C, Oijala M, Soltesz I. Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy. eNeuro. 2014 Dec;1(1):ENEURO.0005-14.2014. doi: 10.1523/ENEURO.0005-14.2014. — View Citation

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503. — View Citation

Theodore WH, Spencer SS, Wiebe S, Langfitt JT, Ali A, Shafer PO, Berg AT, Vickrey BG. Epilepsy in North America: a report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization. Epilepsia. 2006 Oct;47(10):1700-22. doi: 10.1111/j.1528-1167.2006.00633.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	responder rate	proportion of people with a 50% or greater reduction in seizure frequency following the treatment period	8 weeks
Secondary	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
Secondary	scalp electroencephalogram	Routine scalp electroencephalogram at 40 min	8 weeks
Secondary	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
Secondary	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
Secondary	MoCA	Montreal Cognitive Assessment. A max score is 30 points, and a score = 26 is considered normal.	8 weeks
Secondary	MMSE	Mini-Mental State Examination. The normal values are defined as: illiterates >17, primary school >20, junior high school or above >24.	8 weeks
Secondary	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
Secondary	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
Secondary	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