cTBS Targeting Cerebellum for Drug-refractory Epilepsy

• Sponsor: Xijing Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05042726
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 21.5
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This study aims to observe the efficacy, durability and safety of cerebellar continuous θ burst stimulation (cTBS) in the treatment of drug-refractory epilepsy, and to provide a new method for the treatment of drug-refractory epilepsy and improve the quality of life of patients.

This study was a randomized cross-over study. First, the clinical information, imaging, EEG and quality scores of lives of patients with drug-refractory epilepsy were collected, who were continuously enrolled in the Neurology department of Xijing Hospital. Secondly, patients were randomized into groups for cross-over treatment, and the efficacy was analyzed by appropriate statistical methods.

Condition or Disease	Intervention/Treatment	Phase
Drug Refractory Epilepsy	Device: cTBS First; Device: Pseudo-stimulation First	N/A

Detailed Description

θ burst stimulation (TBS) is characterized by plexus stimulation. This mode is that each plexus usually contains three pulses and the frequency of intra plexus pulse is 50Hz while the frequency of interplexus pulse is 5Hz. Continuous θ burst stimulation (cTBS) mainly produces inhibitory effects on the cortex, and the inhibition of motor evoked potentials (MEP) lasts for 60min, which is more durable than traditional rTMS, but the intensity of stimulation is lower and the time of stimulation is shorter.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Continuous Theta Burst Stimulation Targeting Cerebellum for Drug-refractory Epilepsy: A Randomized Cross-over Clinical Study
• Actual Study Start Date: Sep 13, 2021
• Anticipated Primary Completion Date: Jul 14, 2022
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cTBS First The first course of treatment, participants are treated with cTBS for 2 weeks, a total of 10 times, then followed up for 8 weeks. The first course of treatment, participants are treated with pseudo-stimulation for 2 weeks, a total of 10 times, then followed up for 8 weeks.	Device: cTBS First; cTBS: At 30 Hz, the stimulation intensity was 80% resting motor threshold (RMT), and the duration was 33.2 s as a group of stimulation with 600 stimulation pulses. Two groups of stimulation were repeated in each cerebellar hemisphere with an interval of 5 min in each group. Pseudo-stimulation: The operation system has built-in program pseudo-stimulation and other parameters are same as cTBS. The first course of treatment, participants are treated with cTBS for 2 weeks, a total of 10 times, then followed up for 8 weeks. The first course of treatment, participants are treated with pseudo-stimulation for 2 weeks, a total of 10 times, then followed up for 8 weeks.
Experimental: Pseudo-stimulation First The first course of treatment, participants are treated with pseudo-stimulation for 2 weeks, a total of 10 times, then followed up for 8 weeks. The first course of treatment, participants are treated with cTBS for 2 weeks, a total of 10 times, then followed up for 8 weeks.	Device: Pseudo-stimulation First; cTBS: At 30 Hz, the stimulation intensity was 80% resting motor threshold (RMT), and the duration was 33.2 s as a group of stimulation with 600 stimulation pulses. Two groups of stimulation were repeated in each cerebellar hemisphere with an interval of 5 min in each group. Pseudo-stimulation: The operation system has built-in program pseudo-stimulation and other parameters are same as cTBS. The first course of treatment, participants are treated with pseudo-stimulation for 2 weeks, a total of 10 times, then followed up for 8 weeks. The first course of treatment, participants are treated with cTBS for 2 weeks, a total of 10 times, then followed up for 8 weeks.

Outcome Measures

Primary Outcome Measures

1. seizure frequency before recruiting [just before treatment]

   seizures frequency and performance per month before recruiting

2. seizure frequency at the first month after the first treatment course [the first month after the first course of treatment]

   seizures per month and the performance one month after the first treatment course

3. seizure frequency at the second month after the first treatment course [the second month after the first course of treatment]

   seizures per month and the performance two months after the first treatment course

4. seizures frequency at the first month after the second treatment course [the first month after the first course of treatment]

   seizures per month and the performance one month after the second treatment course

5. seizure frequency at the second month after the second treatment course [the second month after the first course of treatment]

   seizures per month and the performance two months after the second treatment course

6. EEG before recruiting [0-5 days before treatment]

   EEG background activity and abnormal waves before recruiting

7. EEG right after the first treatment course [0-3 days after the first treatment course]

   EEG background activity and abnormal waves after the first treatment course, as soon as possible

8. EEG at one month after the first treatment course [one month after the first course of treatment]

   EEG background activity and abnormal waves one month after the first treatment course

9. EEG at two months after the first treatment course [two months after the first course of treatment]

   EEG background activity and abnormal waves two months after the first treatment course

10. EEG right after the second treatment course [0-3 days after the second treatment course]

    EEG background activity and abnormal waves after the second treatment course, as soon as possible

11. EEG at one month after the second treatment course [one month after the first course of treatment]

    EEG background activity and abnormal waves one month after the second treatment course

12. EEG at two months after the second treatment course [two months after the first course of treatment]

    EEG background activity and abnormal waves two months after the second treatment course

Secondary Outcome Measures

1. quality scores before recruiting [before treatment]

   Quality of life in epilepsy (QOLIE-31) will be taken before recruiting. The scale has 31 questions including 8 evaluation factors. And each evaluation factor is based on a percentage scale. Total points=SUM( points in each factor/ question number in the factor)*weight. Then search the form to find the corresponding T value and the higher T value, the better of life quality.

2. quality scores at one month after the first treatment course [one month after the first course of treatment]

   QOLIE-31 will be taken every month in the whole therapy.

3. quality scores at one month after the first treatment course [two months after the first course of treatment]

   QOLIE-31 will be taken every month in the whole therapy.

4. quality scores at one month after the second treatment course [one month after the second course of treatment]

   QOLIE-31 will be taken every month in the whole therapy.

5. quality scores at one month after the second treatment course [two months after the second course of treatment]

   QOLIE-31 will be taken every month in the whole therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Participants who are in line with the diagnostic criteria for epilepsy,
• 1. Participants who are diagnosed as drug-refractory epilepsy,
• 1. Participants who has duration of epilepsy ≥2 years and seizure frequency ≥2 times per month,
• 1. The type and dosage of anti-epileptic drugs do not change during the experiment,
• 1. Participants and their families are aware of this study and sign informed consent.

Exclusion Criteria:

• 1. Participants who are in status epilepticus,
• 1. Participants who are complicated with serious infection, cerebrovascular disease, malignant tumor and other nervous system diseases, and with serious dysfunction of heart, liver, kidney and other organs,
• 1. Participants who are diagnosed as syncope, hysteria or other non-epileptic attacks,
• 1. Participants who are in pregnancy or lactating,
• 1. Participants who have incomplete clinical data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xijing Hospital	Xi'an	Shaanxi	China	710032

Sponsors and Collaborators

• Xijing Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2006 Jan 19.
• 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. Review.
• 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.
• Forsgren L, Beghi E, Oun A, Sillanpää M. The epidemiology of epilepsy in Europe - a systematic review. Eur J Neurol. 2005 Apr;12(4):245-53. Review.
• 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. Review.
• 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.
• 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.
• 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). pii: e.2014.
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9.
• 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.

• Responsible Party: Xijing Hospital
• ClinicalTrials.gov Identifier: NCT05042726
• Other Study ID Numbers: XijingSN
• First Posted: Sep 13, 2021
• Last Update Posted: Dec 1, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Xijing Hospital: Drug Refractory Epilepsy; Continuous θ Burst Stimulation
• Additional relevant MeSH terms: Epilepsy; Drug Resistant Epilepsy

Study Results

No Results Posted as of Dec 1, 2021