Continuous Thetaburst Stimulation for the Treatment of Refractory Epilepsy - Safety, Feasibility and Proof-of-concept

NCT ID: NCT02635633

Last Updated: 2022-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2018-09-30

Brief Summary

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The purpose of this study is to investigate a novel stimulation protocol of repetitive transcranial magnetic stimulation (rTMS) for the treatment of unifocal neocortical epilepsy, namely continuous thetaburst stimulation (cTBS). As this is a pilot study, the primary endpoint is on safety and tolerability of the treatment. However, information on clinical efficacy and mechanism of action will also be collected.

Detailed Description

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1. Study design:

This is an open label prospective pilot trial of continuous thetaburst stimulation (cTBS) in patients with unifocal neocortical epilepsy.

The study comprises a 13-week period, consisting of 4 weeks baseline seizure frequency assessment, a one-week treatment period with baseline assessments on Monday (T0) and stimulation sessions from Tuesday to Friday (T1-T4), and an 8-week follow-up period with short-term assessments immediately after the final stimulation session on Friday afternoon (T4) and long-term assessments after 2 weeks (FU2) and 8 weeks (FU8).
2. Objectives:

The primary objective is to assess the feasibility, safety and tolerability of cTBS in refractory epilepsy patients. The secondary objectives are to assess the clinical efficacy and associated mechanism of action of cTBS in unifocal neocortical epilepsy.
3. Rationale:

An open label prospective design allows to make a first estimate on the safety, feasibility and tolerability of cTBS in refractory epilepsy patients. There are currently no reports available of cTBS performed in epilepsy patients. The ultimate aim is to assess clinical efficacy of cTBS with regard to seizure frequency, but a feasibility and safety study is a prerequisite in order to achieve this goal.

Conditions

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Epilepsies, Partial

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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continuous thetaburst stimulation

Transcranial magnetic stimulation over the epileptogenic focus using a cTBS stimulation protocol.

Group Type EXPERIMENTAL

continuous thetaburst stimulation

Intervention Type DEVICE

On 4 consecutive days patients receive 5 cTBS trains with a 10min intertrain-interval. One cTBS train consists of 600 pulses delivered in bursts at theta frequency (200ms) during 40s. Each burst comprises 3 pulses at 50Hz. Focal stimulation occurs over the epileptogenic focus (EF), perpendicular to the local gyral geometry, using online neuronavigation. Stimulation intensity is set relative to the resting motor threshold (rMT) determined at baseline (80% rMT). Stimulation intensity is further adjusted to the coil-cortex distance at the EF with the following formula: adjusted MT% (AdjMT) = rMT + 2,7\*(DEF-DM1) \[DEF = distance over EF; DM1 = distance over M1\]. If rMT exceeds the capacity of the stimulator output, stimulation intensity is 100% of maximal stimulator output (MSO).

Interventions

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continuous thetaburst stimulation

On 4 consecutive days patients receive 5 cTBS trains with a 10min intertrain-interval. One cTBS train consists of 600 pulses delivered in bursts at theta frequency (200ms) during 40s. Each burst comprises 3 pulses at 50Hz. Focal stimulation occurs over the epileptogenic focus (EF), perpendicular to the local gyral geometry, using online neuronavigation. Stimulation intensity is set relative to the resting motor threshold (rMT) determined at baseline (80% rMT). Stimulation intensity is further adjusted to the coil-cortex distance at the EF with the following formula: adjusted MT% (AdjMT) = rMT + 2,7\*(DEF-DM1) \[DEF = distance over EF; DM1 = distance over M1\]. If rMT exceeds the capacity of the stimulator output, stimulation intensity is 100% of maximal stimulator output (MSO).

Intervention Type DEVICE

Other Intervention Names

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rTMS cTBS

Eligibility Criteria

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Inclusion Criteria

* Refractory unifocal neocortical epilepsy with a well-defined ictal onset zone based on a standardized presurgical evaluation
* ≥ 4 seizures/month, for at least six months
* On a stable drug regimen for at least 2 months
* IQ \>70
* Reliable completion of a seizure diary by patient or caretakers
* Therapeutic compliance in the past
* Informed consent signed

Exclusion Criteria

* Pregnancy, short-term birth wish or childbearing age without adequate birth control
* History of psychogenic non-epileptic seizures
* Intracranial metal hardware (excluding dental filling): surgical clips, shrapnell, electrodes under the stimulation area
* Presence of pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants or deep brain stimulation (DBS)

Patients with a vagus nerve stimulator are not excluded, provided that adequate distance between the coil and the implanted material can be maintained.

As the short duration of the study will not interfere with an ongoing presurgical evaluation and/or its eventual conclusion, the patients in the course of the evaluation or awaiting surgery are also eligible for inclusion.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Kristl Vonck

Prof. Dr. Boon

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kristl Vonck, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

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University Hospital Ghent

Ghent, , Belgium

Site Status

Countries

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Belgium

References

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Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

Reference Type BACKGROUND
PMID: 15664172 (View on PubMed)

Sun W, Mao W, Meng X, Wang D, Qiao L, Tao W, Li L, Jia X, Han C, Fu M, Tong X, Wu X, Wang Y. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia. 2012 Oct;53(10):1782-9. doi: 10.1111/j.1528-1167.2012.03626.x. Epub 2012 Sep 5.

Reference Type BACKGROUND
PMID: 22950513 (View on PubMed)

Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006 Oct;60(4):447-55. doi: 10.1002/ana.20950.

Reference Type BACKGROUND
PMID: 17068786 (View on PubMed)

Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Lagana A, Inghilleri M, Giallonardo AT, Berardelli A, Pacifici L, Ferreri F, Tombini M, Gilio F, Quarato P, Conte A, Manganotti P, Bongiovanni LG, Monaco F, Ferrante D, Rossini PM. Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Epilepsia. 2007 Feb;48(2):366-74. doi: 10.1111/j.1528-1167.2006.00938.x.

Reference Type BACKGROUND
PMID: 17295632 (View on PubMed)

Theodore WH, Hunter K, Chen R, Vega-Bermudez F, Boroojerdi B, Reeves-Tyer P, Werhahn K, Kelley KR, Cohen L. Transcranial magnetic stimulation for the treatment of seizures: a controlled study. Neurology. 2002 Aug 27;59(4):560-2. doi: 10.1212/wnl.59.4.560.

Reference Type BACKGROUND
PMID: 12196649 (View on PubMed)

Nyffeler T, Wurtz P, Luscher HR, Hess CW, Senn W, Pflugshaupt T, von Wartburg R, Luthi M, Muri RM. Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation. Neurosci Lett. 2006 Nov 27;409(1):57-60. doi: 10.1016/j.neulet.2006.09.011. Epub 2006 Oct 17.

Reference Type BACKGROUND
PMID: 17049743 (View on PubMed)

Nyffeler T, Cazzoli D, Hess CW, Muri RM. One session of repeated parietal theta burst stimulation trains induces long-lasting improvement of visual neglect. Stroke. 2009 Aug;40(8):2791-6. doi: 10.1161/STROKEAHA.109.552323. Epub 2009 Jun 11.

Reference Type BACKGROUND
PMID: 19520986 (View on PubMed)

Goldsworthy MR, Pitcher JB, Ridding MC. The application of spaced theta burst protocols induces long-lasting neuroplastic changes in the human motor cortex. Eur J Neurosci. 2012 Jan;35(1):125-34. doi: 10.1111/j.1460-9568.2011.07924.x. Epub 2011 Nov 25.

Reference Type BACKGROUND
PMID: 22118241 (View on PubMed)

Carrette S, Boon P, Klooster D, Van Dycke A, Carrette E, Miatton M, Raedt R, Delbeke J, Meurs A, Vonck K. Continuous theta burst stimulation for drug-resistant epilepsy. Front Neurosci. 2022 Aug 17;16:885905. doi: 10.3389/fnins.2022.885905. eCollection 2022.

Reference Type DERIVED
PMID: 36061598 (View on PubMed)

Other Identifiers

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EC/2015/0596

Identifier Type: -

Identifier Source: org_study_id

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