Drug Refractory EpilepsyNCT05042726
cTBS Targeting Cerebellum for Drug-refractory Epilepsy
A study testing cTBS First and Pseudo-stimulation First in people with Drug Refractory Epilepsy, run by Xijing Hospital at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Drug Refractory Epilepsy
- What is being tested?
- cTBS First and Pseudo-stimulation First
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteChina
- Study dates
- 2 Aug 2021to 26 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bilateral Continuous Theta Burst Stimulation of Cerebellum for Drug-refractory Epilepsy: A Double Blind, Randomised, Single Centre, Crossover Clinical Trial
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.
- Conditions
- Drug Refractory Epilepsy
- Being tested
- cTBS First, Pseudo-stimulation First
- Keywords
- Drug Refractory Epilepsy, Continuous θ Burst Stimulation, Cerebellar Dentate Nucleus
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cTBS FirstDevice
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.
Pseudo-stimulation FirstDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| cTBS First | Experimental | 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. Receives: Device: cTBS First |
| Pseudo-stimulation First | Experimental | 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. Receives: Device: Pseudo-stimulation First |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 weeks
responder rate
proportion of people with a 50% or greater reduction in seizure frequency following the treatment period
Measured: 8 weeks
Secondary outcomes (9)
QOLIE-31 scale scores
Quality of Life in Epilepsy-31. Scores range from 0 to 100, with higher scores indicating better quality of life.
Measured: 8 weeks
scalp electroencephalogram
Routine scalp electroencephalogram at 40 min
Measured: 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.
Measured: 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.
Measured: 8 weeks
MoCA
Montreal Cognitive Assessment. A max score is 30 points, and a score ≥ 26 is considered normal.
Measured: 8 weeks
MMSE
Mini-Mental State Examination. The normal values are defined as: illiterates >17, primary school >20, junior high school or above >24.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2021
- Study start2 Aug 2021
- Primary completion24 Aug 2022
- Study completion26 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Drug Refractory EpilepsyStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05042726
- Sponsor's protocol ID
- XijingSN
- Status last verified
- Aug 2022
- First submitted
- 31 Aug 2021
- Last updated
- 5 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17054693Forsgren 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.
PubMed 15804240Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.
PubMed 10660394George 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.
PubMed 19693003Hsu 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.
PubMed 21715144Cooper 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.
PubMed 29588988Chung 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.
PubMed 26850210Koc 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.
PubMed 29073474Brighina 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.
PubMed 16426754Krook-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.
PubMed 25599088
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bilateral Continuous Theta Burst Stimulation of Cerebellum for Drug-refractory Epilepsy: A Double Blind, Randomised, Single Centre, Crossover Clinical Trial
- ClinicalTrials.gov ID
- NCT05042726
- Acronym / sponsor ID
- XijingSN
- Conditions
- Drug Refractory Epilepsy
- Keywords
- Drug Refractory Epilepsy, Continuous θ Burst Stimulation, Cerebellar Dentate Nucleus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- 2 Aug 2021 (actual)
- Primary completion
- 24 Aug 2022 (actual)
- Study completion
- 26 Aug 2022 (actual)
- First posted
- 13 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cTBS First | Experimental | Device: cTBS FirstThe 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. |
| Pseudo-stimulation First | Experimental | Device: Pseudo-stimulation FirstThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cTBS FirstContinuous 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. | Device | cTBS First |
| Pseudo-stimulation FirstThe 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. | Device | Pseudo-stimulation First |
Primary outcome
seizure reduction rate in pre- and post-treatment
Time frame: 8 weeks
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
responder rate
Time frame: 8 weeks
proportion of people with a 50% or greater reduction in seizure frequency following the treatment period
9 secondary outcomes
QOLIE-31 scale scores
Time frame: 8 weeks
scalp electroencephalogram
Time frame: 8 weeks
IQ
Time frame: 8 weeks
MQ
Time frame: 8 weeks
MoCA
Time frame: 8 weeks
MMSE
Time frame: 8 weeks
HAMD
Time frame: 8 weeks
HAMA
Time frame: 8 weeks
SCL-90
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2023.
- Background: PubMed 17054693Theodore 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.
- Background: PubMed 15804240Forsgren 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.
- Background: PubMed 10660394Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.
- Background: PubMed 19693003George 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.
- Background: PubMed 21715144Hsu 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.
- Background: PubMed 29588988Cooper 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.
- Background: PubMed 26850210Chung 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.
- Background: PubMed 29073474Koc 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.
- Background: PubMed 16426754Brighina 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.
- Background: PubMed 25599088Krook-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cTBS First and Pseudo-stimulation First in people with Drug Refractory Epilepsy, run by Xijing Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
seizure reduction rate in pre- and post-treatment (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05042726, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2023.