NCT03154307

Brief Summary

Perform non-invasive neuro-navigated repeated Transcranial Magnetic Stimulation (rTMS) at low frequencies (LF) with the intent to reduce the occurrence of seizures over time (long-term protocol). Seizure reduction and improvements in the quality of life in patients with epilepsy will be associated with increased cortical inhibition resulting from the LF-rTMS sessions over time. This procedure using rTMS at low frequencies (LF-rTMS) between 0.5 and 1 Hz is a safe and painless method for noninvasive focal cortical brain stimulation, which will be evaluated in its efficacy at reducing/suppressing seizures. Accordingly, we propose a clinical trial in patients with epilepsy to test whether LF-rTMS can improve seizure suppression. The location of the presumed 3D source in the brain will be stimulated for few minutes (10 to 15 min.). With the same rTMS modality, we will also perform motor threshold mapping in conjunction with its fully integrated and compatible electroencephalography (EEG) module. Up to 100 individuals 18 to 80 years with epilepsy will be enrolled. In addition, a short-term protocol has been added to test whether LF-rTMS can reduce or suppress status epilepticus in medically refractory participants.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Feb 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 19, 2016

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

May 10, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 16, 2017

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 23, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 23, 2019

Completed
3.8 years until next milestone

Results Posted

Study results publicly available

June 23, 2023

Completed
Last Updated

June 23, 2023

Status Verified

May 1, 2023

Enrollment Period

3.5 years

First QC Date

May 10, 2017

Results QC Date

November 9, 2022

Last Update Submit

May 31, 2023

Conditions

EpilepsyStatus EpilepticusEpilepsia Partialis ContinuaEpilepsia Partialis Continua, Refractory (Medically)

Outcome Measures

Primary Outcomes (3)

  • Average Weekly Seizure Frequency

    Seizure frequency was recorded by the caregiver in a journal at weeks 6 and 7 post rTMS treatment.

    6 and 7 weeks post rTMS treatment

  • Scalp EEG: Number of Interictal Epileptiform Discharges

    Interictal discharges are common in those with epilepsy and tends to decrease with treatment.

    From start of intervention through 5 days of treatment

  • Seizure Duration Proxy for Seizure Severity

    Care provider journaled the seizure duration over the coure of a 2-week period beginning on week 6 post rTMS treatment.

    6-7-weeks post rTMS treatment

Secondary Outcomes (5)

  • Interhemispheric EEG Asymmetry Ratio for Alpha Power

    8-weeks Post rTMS Treatment

  • Scalp EEG Functional Connectivity for Alpha Hz

    8-weeks Post rTMS Treatment

  • Abductor Pollicis Brevis (APB)-Evoked Response Threshold

    8-weeks Post rTMS treatment

  • Treatment Response Rate

    8-weeks post rTMS treatment

  • Intrahemispheric EEG Asymmetry Ratio for Alpha Power

    8-weeks Post rTMS Treatment

Study Arms (4)

Group 1: Weekly TMS

EXPERIMENTAL

LF-rTMS intervention for 2 weeks (5 days per week for total of 10 days) , LF-rTMS 1 session/week for 1 month (4 days), and LF-rTMS 1 session/month for 11 months

Device: Low frequency repeated TMS (LF-rTMS)

Group 2: Monthly TMS

EXPERIMENTAL

LF-rTMS intervention for 2 weeks (5 days per week for total of 10 days), LF-rTMS 1 session/month for 12 months

Device: Low frequency repeated TMS (LF-rTMS)

Group 3: Sham TMS

SHAM COMPARATOR

Sham LF-rTMS for 2 weeks (5 days per week for a total of 10 days), sham LF-rTMS 1 session/week for 1 month (4 days), and sham LF-rTMS 1 session/month for 1 month. After the sham stimulation real LF-rTMS intervention sessions will be delivered as follows: 50% of placebo group will follow group 1 protocol and the other 50% will follow group 2 protocol

Device: Low frequency repeated TMS (LF-rTMS)

Short-term protocol

EXPERIMENTAL

LF-rTMS intervention daily for up to 5 days in medically refractory status epilepticus participants only

Device: Low frequency repeated TMS (LF-rTMS)

Interventions

Low frequency repeated TMS (LF-rTMS)DEVICE

Each patient will then begin treatment with 14 minute sessions of 1 Hz rTMS or sham rTMS, 120% minimum threshold (MT), and 800 stimuli on the position of the calculated 3D source using EEG, MRI, and digitized electrode locations. Two different timelines of delivering the rTMS will be compared against a sham/delayed treatment group.

Group 1: Weekly TMSGroup 2: Monthly TMSGroup 3: Sham TMSShort-term protocol

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Experience ≥ 3 seizures/month in the month prior to starting study (any type of seizure will count)
  • No status epilepticus in the last 12 months
  • No change in medication in last 30 days

You may not qualify if:

  • Presence of implanted electronic devices (e.g., pacemaker, medication pump, brain or vagus nerve stimulator, cochlear implant)
  • Presence of intracranial metal (e.g., aneurysm clip)
  • Unable to cooperate with non-sedated, navigated TMS testing
  • Short-term protocol:
  • Epilepsia partialis continua or status epilepticus
  • At least 2 medications failed
  • At least 24 hours of acute phase
  • Presence of implanted electronic devices (e.g., pacemaker, medication pump, brain or vagus nerve stimulator, cochlear implant)
  • Presence of intracranial metal (e.g., aneurysm clip)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

Related Publications (7)

  • Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation in neurology. Lancet Neurol. 2003 Mar;2(3):145-56. doi: 10.1016/s1474-4422(03)00321-1.

    PMID: 12849236BACKGROUND

  • Hallett M. Transcranial magnetic stimulation and the human brain. Nature. 2000 Jul 13;406(6792):147-50. doi: 10.1038/35018000.

    PMID: 10910346BACKGROUND

  • Rossini PM, Rossi S. Transcranial magnetic stimulation: diagnostic, therapeutic, and research potential. Neurology. 2007 Feb 13;68(7):484-8. doi: 10.1212/01.wnl.0000250268.13789.b2.

    PMID: 17296913BACKGROUND

  • Siebner HR, Hartwigsen G, Kassuba T, Rothwell JC. How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition. Cortex. 2009 Oct;45(9):1035-42. doi: 10.1016/j.cortex.2009.02.007. Epub 2009 Mar 3.

    PMID: 19371866BACKGROUND

  • Udupa K, Sathyaprabha TN, Thirthalli J, Kishore KR, Raju TR, Gangadhar BN. Modulation of cardiac autonomic functions in patients with major depression treated with repetitive transcranial magnetic stimulation. J Affect Disord. 2007 Dec;104(1-3):231-6. doi: 10.1016/j.jad.2007.04.002. Epub 2007 May 8.

    PMID: 17490754BACKGROUND

  • Fox MD, Liu H, Pascual-Leone A. Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity. Neuroimage. 2013 Feb 1;66:151-60. doi: 10.1016/j.neuroimage.2012.10.082. Epub 2012 Nov 7.

    PMID: 23142067BACKGROUND

  • Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.

    PMID: 24411682BACKGROUND

MeSH Terms

Conditions

EpilepsyStatus EpilepticusEpilepsia Partialis Continua

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesSeizuresNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Clinical Research Administrator
Organization
Miami Neuroscience Institute
starlieb@baptisthealth.net
17865961825

Study Officials

  • Alberto Pinzon, M.D., Ph.D.

    Baptist Health South Florida

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
Participant and outcomes assessor will be masked in the 3 arms of the long-term protocol. However, the short-term arm will be open label.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Neurologist, Medical Director, Baptist Health Epilepsy Program

Study Record Dates

First Submitted

May 10, 2017

First Posted

May 16, 2017

Study Start

February 19, 2016

Primary Completion

August 23, 2019

Study Completion

August 23, 2019

Last Updated

June 23, 2023

Results First Posted

June 23, 2023

Record last verified: 2023-05

Locations

US(1)