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Safety and Therapeutic Measures of Tdcs in Patients With Refractory Focal Epilepsy

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ClinicalTrials.gov Identifier: NCT02866240
Recruitment Status : Unknown
Verified July 2017 by Neuroelectrics Corporation.
Recruitment status was:  Recruiting
First Posted : August 15, 2016
Last Update Posted : July 13, 2017
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Boston Children’s Hospital
Information provided by (Responsible Party):
Neuroelectrics Corporation

Brief Summary:

This is a single site, non-randomized, prospective, open-label, interventional pilot/feasibility study. Patients recruited will have medically-refractory focal neocortical epilepsy, defined on the basis of presence of focal spikes and (if available) focal seizure onsets originating from the lateral cortical surface of any lobe. Patients will be recruited from the epilepsy clinics of Boston Children's Hospital (BCH) and Beth Israel Deaconess Medical Center (BIDMC), the home institutions of the principal investigators. All patients and referring physicians will be requested to maintain their current antiepileptic drugs throughout the study with changes after enrollment permitted only to maintain pre-enrollment drug levels, or if clinically necessary. The primary outcome measure will be the change in seizure frequency (seizures/4-week period) as compared to baseline. Secondary outcome measures include change in interictal discharge burden, change in cortical excitability, and quality of life measures.

Patients with medically-refractory neocortical epilepsy will receive cathodal tDCS administered to the seizure focus for 10 sessions over a 2-week period with the allowance of make-up sessions in week three. Subjects will be evaluated at baseline, during the stimulation sessions, and 4 and 8 weeks after the completion of the tDCS visits


Condition or disease Intervention/treatment Phase
Refractory Epilepsy Device: Cathodal Transcranial Direct Current Stimulation (tDCS). Not Applicable

Detailed Description:

Noninvasive neurostimulation techniques include Transcranial magnetic stimulation (TMS) and Cathodal Transcranial Direct Current Stimulation (tDCS). Of these, tDCS is uniquely suited to mass distribution and treatment, even at home, as it is lightweight, portable, inexpensive and has a favorable safety profile. In tDCS, a low intensity (1-2 mA) unidirectional electrical current is applied to the scalp to influence underlying cortical excitability. Some small preliminary studies suggest that cathodal tDCS may suppress epileptic seizures [1,2]. However, a well-powered randomized-controlled trial demonstrating convincing proof of efficacy has not been conducted. This study is intended to test whether tDCS reduces seizures in patients with intractable focal neocortical epilepsy. The hypothesis is that repeated daily sessions of cathodal tDCS will lead to a clinically significant decrease in seizures in this population. Successful completion of this pilot study will be an essential first step toward a larger placebo-controlled trial with the goal of establishing cathodal tDCS as a novel, non-invasive and inexpensive treatment for drug-resistant seizures, and will provide the critical data needed for an application to obtain FDA approval for the use of tDCS in the treatment of drug-resistant epilepsy.

tDCS is a painless method for focal brain stimulation. tDCS is based on decades-old observations that neuronal firing is modulated by low amplitude electrical direct current (DC). Specifically, when applied to the cerebral cortex, cathodal DC inhibits neuronal firing [3,4]. The mechanisms by which cathodal DC reduces neuronal firing likely relate to hyper‐polarization of the soma membrane which occurs when the apical dendrites neuron are oriented toward the cathode in a constant electric field [5]. The practical application of tDCS is simple: low amplitude DC is administered via scalp electrodes such that the cerebral cortex is exposed to cathodal DC beneath one of the electrodes, and the return (anodal) electrodes can be placed anywhere else on the body, or in more complex arrangements to minimize currents at any one site. tDCS methods have also recently been adapted to rats for work with disease models showing success with seizure suppression [6,7]. Hundreds of tDCS trials have demonstrated the technique to be well tolerated and safe. Direct electrical current stimulation is presently FDA-approved for extracranial use, and FDA applications for cranial stimulation (tDCS) for management of mood disorder and chronic pain are in progress. tDCS units are also inexpensive and light-weight. The electrical supply can be derived from conventional 9-volt batteries. The scalp electrodes can be fastened in seconds. tDCS can be combined easily with other therapies, such as those that may be required for resuscitation of an acutely-injured patient. tDCS is presently under investigation as a treatment for epilepsy, where excess cortical excitability is a prominent feature of the disease process, and where neuronal inhibition may be beneficial. Thus for epilepsy, tDCS may offer a practical non-pharmacologic therapy for the large minority, approximately 35%, of patients whose seizure cannot be controlled by medication.

The tDCS stimulator used in this clinical study is the STARSTIM device (Neuroelectrics, Inc). STARSTIM is capable of recording EEG before, during and after tDCS stimulation, and will not only allow for a detailed understanding of the tDCS-induced effect on neural activity, but may eventually serve as a guidance to fine-tune the stimulation parameters and improve the tDCS protocol based on the developmental, behavioral, dynamical, and disease state through closed-loop systems.

Starstim device is remotely controlled using NIC software that stands for Neuroelectrics Instrument Controller (NIC). This application will allow physicians to configure the study protocol with all the defined parameters. The provided version of software will only enable to apply tDCS protocols to the subjects in the study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Therapeutic Measures of Cathodal Transcranial Direct Current Stimulation (Tdcs) in Patients With Refractory Focal Epilepsy
Actual Study Start Date : June 21, 2017
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : January 2018


Arm Intervention/treatment
Experimental: Single arm
Cathodal Transcranial Direct Current Stimulation (tDCS)
Device: Cathodal Transcranial Direct Current Stimulation (tDCS).
Transcranial direct current stimulation (tDCS) is a form of neurostimulation which uses constant, low current delivered to the brain area of interest via electrodes on the scalp.




Primary Outcome Measures :
  1. Seizure frequency in patients with intractable focal neocortical epilepsy using cathodal tDCS. [ Time Frame: 16 weeks ]
  2. Improvement in quality of life (QOL) and cognition in patients with Epilepsy having [ Time Frame: 16 weeks ]
  3. Improvement in quality of life (QOL) in patients with Epilepsy having cathodal tDCS through NIH Toolbox® Emotion Battery. [ Time Frame: 16 weeks ]
  4. Frequency of interictal epileptiform discharges burden in patients with epilepsy having cathodal tDCS. [ Time Frame: 16 weeks ]
  5. Change in cortical excitability measures in patients with epilepsy having cathodal tDCS, and correlation with seizure outcomes . [ Time Frame: 16 weeks ]
  6. Improvement in cognition in patients with Epilepsy having cathodal tDCS through NIH Toolbox® Cognition Battery. [ Time Frame: 16 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   9 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 9 years old or older
  • An established diagnosis of medically-refractory neocortical epilepsy (as determined by the referring clinician), with a clearly defined seizure focus.
  • Diagnosis of epilepsy with focal seizures with or without secondary generalization (International League Against Epilepsy classification). Diagnosis established by clinical history and an electroencephalogram consistent with localization-related epilepsy.
  • Continued seizures despite adequate dosage in trials of at least 2 or more antiepileptic medications within approximately the last 3 years.
  • At least one clearly identified and localizable epileptogenic zone from which 80% or more seizures arise, as defined by the referring clinician.
  • Currently on 1-4 anti-epileptic drugs (AEDs) with no changes in antiepileptic drug doses in the 3 weeks prior to enrollment in the study and no planned dose changes during the trial and through the primary endpoint
  • A clinical or research MRI scan that is suitable for navigated brain stimulation (NBS) and generation of electrical fields
  • A reported average of at least 3 seizures per month (focal or secondarily generalized) over the three months prior to enrollment, and a minimum of 4 seizures recorded during the 8-week baseline period, with no 21-day seizure-free period during the 8 week baseline
  • Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

  • Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. All female participants of child bearing age are required to have a pregnancy test. Additionally, all females of childbearing potential will be required to use an effective method of birth control including: oral hormonal contraceptives; implanted hormonal contraceptives, diaphragm with spermicide; condoms; intra-uterine device; abstinence.
  • Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  • Uncertainty regarding the diagnosis of medically-refractory epilepsy.
  • History of Non-epileptic or psychogenic seizures, Primary generalized seizures, Status epilepticus in the last 12 months, Suspicion for or a significant history of syncope, Coexisting significant medical condition that is not in good control, Progressive neurologic disease, Progressive brain disorders, Serious systemic diseases, Symptomatic cerebrovascular disease, Cardiac disease, Chronic skin disease or Damaged skin on scalp that would interfere with tDCS stimulation.
  • Any cranial metal implants (excluding dental fillings) or medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagus nerve stimulator).
  • Previous surgeries opening the skull.
  • Active or recent substance abuse or dependence within the past year.
  • No medication is an absolute exclusion from tDCS/TMS. Medications will be reviewed and a decision about inclusion will be made based on the following: patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other central nervous system (CNS) active drugs. The published TMS guidelines review of medications to be considered with TMS will be taken into consideration.
  • Any condition that makes the subject, in the opinion of the investigator, unsuitable for the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866240


Contacts
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Contact: Alex Rotenberg, M.D., Ph.D. 617-730-0463 alexander.rotenberg@childrens.harvard.edu

Locations
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United States, Massachusetts
Boston Children´S Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: ALEXANDER ROTENBERG, MD, PHD    617-355-6000    alexander.rotenberg@childrens.harvard.edu   
Sub-Investigator: MOUHSIN SHAFI, MD,PHD         
Sponsors and Collaborators
Neuroelectrics Corporation
Beth Israel Deaconess Medical Center
Boston Children’s Hospital
Investigators
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Principal Investigator: Alex Rotenber, M.D., Ph.D. Boston Children’s Hospital

Publications of Results:

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Responsible Party: Neuroelectrics Corporation
ClinicalTrials.gov Identifier: NCT02866240     History of Changes
Other Study ID Numbers: BCHEpilepsy
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:
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Epilepsy
Drug Resistant Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases