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

NCT02635633 | Terminated DMC

• 1 other identifier: EC/2015/0596
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Epilepsies, Partial

Keywords

partial epilepsy; unifocal neocortical; treatment resistant; transcranial magnetic stimulation; thetaburst stimulation

Outcome Measures

Primary Outcomes (1)

• Seizure induction

  Induction of epileptic seizures during or in-between rTMS stimulation trains as a measure of safety

  Throughout stimulation, 4 days

Secondary Outcomes (16)

• Seizure diary

  Throughout the study, lasting 13 weeks

• Adverse events diary

  Throughout the study, lasting 13 weeks

• Number of interictal epileptiform discharges (IEDs) on hd-EEG

  Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)

• Number of interictal epileptiform discharges (IEDs) on normal EEG

  Throughout the study, lasting 13 weeks: assessment immediately before and after each treatment session

• Cortical resting motor threshold (rMT)

  Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)

Study Arms (1)

continuous thetaburst stimulation

EXPERIMENTAL

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

Device: continuous thetaburst stimulation

Interventions

continuous thetaburst stimulation 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).

Also known as: rTMS, cTBS

continuous thetaburst stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

University Hospital Ghent

Ghent, 9000, Belgium

Location

Related Publications (9)

• 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.

  PMID: 15664172 BACKGROUND

• 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.

  PMID: 22950513 BACKGROUND

• 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.

  PMID: 17068786 BACKGROUND

• 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.

  PMID: 17295632 BACKGROUND

• 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.

  PMID: 12196649 BACKGROUND

• 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.

  PMID: 17049743 BACKGROUND

• 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.

  PMID: 19520986 BACKGROUND

• 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.

  PMID: 22118241 BACKGROUND

• 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.

  PMID: 36061598 DERIVED

MeSH Terms

Conditions

Epilepsies, Partial

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Kristl Vonck, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Boon

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: December 21, 2015
• Study Start: August 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: September 1, 2018
• Last Updated: February 15, 2022

Record last verified: 2022-01

Locations

BE (1)