Clinical trial NCT04770337: Pivotal-Safety and Therapeutic Measures of tDCS in Patients With Refractory Focal Epilepsy
Official title: STARSTIM: SAFETY AND THERAPEUTIC MEASURES OF TRANSCRANIAL CATHODAL DIRECT CURRENT STIMULATION (TDCS) IN PATIENTS WITH REFRACTORY FOCAL EPILEPSY
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Refractory Epilepsy
Focal Seizure
Seizures, Focal
Seizures
Epilepsy in Children
Epilepsy
Epilepsy, Tonic-Clonic
Keywords: Epilepsy
Focal seizure
Seizure
Lead sponsor: Neuroelectrics Corporation
Sponsor class: INDUSTRY
First posted: 2021-02-25
Enrollment: 190
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multiple site, randomized, double blinded parallel-group controlled study
Primary purpose: TREATMENT

Brief summary: This is a multiple site, randomized, double blinded parallel-group controlled study. The purpose of this study is to evaluate efficacy, safety, and tolerability of repeated, daily sessions with the STARSTIM device, which delivers transcranial cathodal direct current stimulation (tDCS). Subjects will be treated with STARTSTIM or sham device for 10 sessions over a 2-week period. The subjects will be followed for an additional 10 weeks post treatment. Quality of Life questionnaires and adverse events will be collected and evaluated.

Detailed description: Study design is an evaluation of the STARSTIM device (tDCS) in subjects over 9 years of age, diagnosed with epilepsy with focal seizures with or without focal to bilateral tonic clonic seizures. Seizure diaries will be collected for 12 weeks to establish a rate of seizure for each subject prior to treatment. Subjects will be randomized in a 1:1 ratio to receive an active STARSTIM treatment or a sham treatment. Neither the study investigator nor subject shall be notified of the treatment assignment. Treatment will be done daily at the investigator's site for 10 days. A Seizure Diary will be maintained through the course of the treatment and the follow up period. Subjects will have 3 follow up visits to evaluate their seizure rate, adverse events, medications and quality of life. A Data Safety Monitoring Board will be utilized to evaluate safety events through study milestones. Seizure frequency rates pre, during and post treatment will be evaluated for both the active and sham treatment arms.

Eligibility criteria: Inclusion Criteria:

1. 9 years old or older
2. Diagnosis of epilepsy with focal seizures with or without focal to bilateral tonic clonic seizures (International League Against Epilepsy classification). Diagnosis established by both clinical history and an EEG consistent with focal seizures.

   Note: A normal interictal EEG is consistent with focal seizures, if other data is adequate to provide localization.
3. Epilepsy is refractory to treatment, defined as: failure to achieve adequate seizure control despite demonstrated compliance, according to medical records, on at least two (2) FDA-approved ASDs at a daily dose considered therapeutic for the patient's demographic according to package labeling, within approximately the last 3 years.
4. Seizure frequency ≥3 per month, over the past year.
5. Currently on ≥1 ASDs with no changes in antiepileptic drug doses in the 3 weeks prior to baseline visit in the study and no planned dose changes during the trial. Changes after baseline visit are permitted only if clinically necessary.
6. An MRI scan of the brain using 1.5 Tesla magnet, or greater, with T1, T2, and FLAIR sequences, performed within past 3 years and more recently than any craniotomy or skull burr hole procedure.
7. Seizure focus that allows design of an appropriate stimulation montage. Note: Seizure focus can be identified within a lobe, or 2 adjacent lobes. Identification of the border of the seizure focus can be approximate (+/- 2 gyri).
8. Available seizure history and supporting data
9. All female study subjects 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 (defined as having a documented failure rate of \<=1%; for women using enzyme-inducing ASDs hormonal contraceptives will not be considered as effective).
10. Written informed consent obtained from study subject or subject's legal representative and ability for study subject to comply with the requirements of the study.
11. Assent from pediatric subjects when appropriate.

Exclusion Criteria:

1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the integrity of the data.
2. Evidence for more than one seizure focus. (NOTE: For this study, a seizure focus is defined as a cortical region confined to one hemisphere and either one lobe or on a junction of two adjacent lobes from which seizures arise , as documented by scalp or intracranial EEG, that is either supported or not refuted by MRI, and either supported or not refuted by clinical semiology). If the interictal EEG is normal, a seizure focus may be identified by the combination of structural findings on MRI and clinical signs/symptoms associated with the subject's seizures.
3. Seizure focus is one of: interhemispheric, cingulate, or orbitofrontal
4. Seizure focus is hemispheric or poorly defined
5. History of psychogenic nonepileptic seizures in past 2 years, or physiologic nonepileptic seizures and non-epileptogenic events, including suspicion for or a significant history of syncope, and any non-epileptic events must be clearly differentiable from subject's focal seizures based on previously recorded video EEG showing distinct clinical and electrographic features of the subject's PNES compared to their epileptic seizures.
6. Seizures of generalized onset
7. Status epilepticus in the last 12 months
8. Presence of any disease, medical condition or physical condition that, in the opinion of the Investigator, may compromise interfere, limit, affect or reduce the subject's ability to complete a study of 24 weeks duration
9. Presence of any disease, medical condition or physical condition that, in the opinion of the Investigator, may adversely impact the safety of the subject or the integrity of the data.
10. Damaged skin on scalp that may interfere with tDCS stimulation.
11. Pregnant or unwilling to practice birth control during participation in the study.
12. Nursing mothers.
13. Any cranial metal implants (excluding ≦1 mm thick epicranial titanium skull plates and dental fillings) or medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant). Note: Vagus nerve stimulator (VNS) is allowable if the device is in MR Mode (e.g. switched off) during tDCS stimulation and the VNS device is MR conditional.
14. Previous surgeries opening the skull leaving skull defects capable of allowing the insertion of a cylinder with a radius greater or equal to 5 mm.
15. A history of addiction to, dependence on, abuse of, misuse of, distribution of, or use of any illicit substance.

Primary outcomes:
measure: The difference between active treatment and sham treatment in the percentage change
timeFrame: from baseline in seizures over the 12 weeks following initiation of treatment.
Secondary outcomes:
measure: The proportion of subjects who are responders (defined as subjects with a 50% or greater reduction in seizure frequency
timeFrame: from baseline to week 12 post-treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute, St. Joseph's Hospital & Medical Center
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: Keck Medicine of USC
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Jacksonville
country: United States
facility: University of Florida Jacksonville
state: Florida
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Baltimore
country: United States
facility: Sinai Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital Comprehensive Epilepsy Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School (Rutgers)
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania (Penn Epilepsy)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University Of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital, University of Washington
state: Washington
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Lyon
country: France
facility: Hospices Civils De Lyon
city: Marseille
country: France
facility: CHU de Marseille - Hôpital de la Timone
city: Albacete
country: Spain
facility: Hospital Universitario Albacete
city: Barcelona
country: Spain
facility: HM Nou Delfos
city: Barcelona
country: Spain
facility: Hospital Clínic
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Niño Jesús
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Sevilla
country: Spain
facility: Centro de Neurología Avanzada
Study officials:
References: