Safety and Therapeutic Measures of Tdcs in Patients With Refractory Focal Epilepsy
Safety and Therapeutic Measures of Tdcs in Patients With Refractory Focal Epilepsy
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. 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/week) as compared to baseline.

 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 8 weeks after the completion of the tDCS visits
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.
 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. 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. 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. Numerous of tDCS studies
 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 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.
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