Clinical trial NCT03747601: Temporal Interference Brain Stimulation
Official title: The Development and Human Translation of Temporal Interference Brain Stimulation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Visual Acuity
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2018-11-20
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The primary aim of this study is to translate temporal interference (TI) stimulation methodology into humans and examine its safety, feasibility, steerability, and focality. In the proposed early phase human experiment, the ability to apply TI stimulation will be assessed along spatial dimensions to selectively modulate neural activity and assess the feasibility of selective targeting deep brain structures without exciting overlaying cortex. The overall goal of the study is to advance TI methodology and its translation to humans.

The specific aims in this study are to

* Assess the safety of TI stimulation.
* Assess the feasibility, focality, and steerability of TI stimulation by selectively modulating activity in subregions of a cortical area (calcarine cortex)

It is hypothesized that TI stimulation can be used to impact different regions of the visual field that are represented within the calcarine fissure of the human brain.

It is hypothesized that TI will be well tolerated by human subjects and side effects will be consistent with other forms of transcranial electric current stimulation (tES).

Detailed description: This is an investigational early phase testing of temporal interference (TI) stimulation in humans. The overall aim of the study is to assess the safety, feasibility, focality, and steerability of TI stimulation by selectively modulating activity in subregions of a cortical area (calcarine cortex - the primary visual cortex)

Healthy subjects who meet inclusion and exclusion criteria will be entered into the study. The study will recruit up to 20 subjects with the aim to complete 12 subjects.

Study Visits:

The study will consist of up to 6 study visits. The screening and baseline visit, the MRI visit, and up to 4 TI study. The screening and baseline visit and TI visits will occur at Beth Israel Deaconess Medical Center in the Berenson-Allen Center. The MRI visit will take place at the Boston University Cognitive Neuroimaging Center. After Informed Consent is obtained, the following screening and baseline procedures will be completed:

* Inclusion and exclusion criteria review
* Subject demographics
* Handedness assessment
* Medical history and medication review
* Physical and Neurological exam conducted by a Neurologist or Neurologic Nurse Practitioner
* Baseline perimetry assessment
* Baseline EEG
* The Mini International Neuropsychiatric Interview (MINI) assessment
* All female subjects will undergo a pregnancy test and pregnant women will be excluded
* Screening for retinotopic mapping - assessing the participant's ability to hold fixation with their eyes for experimental trials
* MRI safety review

The MRI session will take place at the Boston University Cognitive Neuroimaging Center under a Boston University submitted and approved protocol that is specific to this study. An MRI scan of the brain will be conducted while the participant views visual stimuli to obtain each individual's retinotopic map. This data will be provided to the study team at Beth Israel Deaconess Medical Center (BIDMC) to conduct the study visit and for analysis.

Each subject will then undergo up to 4 TI stimulation sessions (2 minimum) separated by at least 2 days to minimize the risk of carry over effects of the stimulation. In each visit, the participant will receive TI stimulation to one of four regions of retinotopic representation in the calcarine fissure:

1. peripheral visual field in the deep region of the fissure
2. foveal visual field in the polar region of the fissure
3. superior quadrant of the visual field in the lower bank of the fissure
4. inferior quadrant of the visual field in the upper bank of the fissure The cortical targets will be defined by electrical field modelling that will be used to optimize the electrode placement. Regions #1 and #2 will be stimulated in the first two visits with the order of stimulation regions to be counterbalanced between participants. If an effect is noted, participants will be asked to complete the additional 2 visits in which regions #3 and #4 will be stimulated.

Each visit will consist of up to 4 blocks of stimulation paired with a visual discrimination task and assessment of visual disturbance with an Amsler grid. The stimulation blocks will each be completed at a different frequency - a control stimulation where TI visual effect is not anticipated (e.g 2 or 20 hertz (Hz)), a no offset stimulation (e.g. matched carrier stimulation frequencies such as no envelope modulation is anticipated) and up to 2 frequencies ranging from 8 to 12. The most common signal from visual cortex during wakeful relaxation is in the frequency range (8-12 Hz). It is hypothesized that TI with a residual effective stimulation frequency of 1-20 Hz will be ideally suited for activation of the targeted visual cortex.

Participants will be monitored throughout he visit for any adverse effects and a tES side-effect questionnaire will be administered at the beginning and end of each stimulation visit to additionally track any adverse effects. Although any visual disruption induced by the stimulation is expected and anticipated to be transient in nature, a visual perimetry assessment will be completed to compare to baseline.

Eligibility criteria: Inclusion Criteria:

* Normal healthy volunteer
* 18-35 years of age
* Normal vision
* Right handed

Exclusion Criteria:

* Corrected-to-Normal vision, or visual impairment.
* Any current or past history of a psychiatric disorder
* Any current or past history of neurological disorders or acquired neurological disease (e.g. stroke, traumatic brain injury), including intracranial lesions
* History of head trauma resulting in prolonged loss of consciousness; or a history of \>3 grade I concussions
* Current history of poorly controlled headaches including intractable or poorly controlled migraines
* Any systemic illness or unstable medical condition that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
* History of fainting spells of unknown or undetermined etiology that might constitute seizures
* History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or family history of treatment resistant epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
* Possible pregnancy. All female participants of child bearing age are required to have a pregnancy test
* Any metal in the brain, skull or elsewhere unless approved by the responsible MD
* Any medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD
* Substance abuse or dependence within the past six months
* Pregnancy; all female participants of child bearing age will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.
* Not on any medications with the exception of birth control unless approved by the responsible MD.

Primary outcomes:
measure: Participants With a Change in Their Visual Field
timeFrame: Immediately after intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References: