Temporal Interference Brain Stimulation (TI)

• ClinicalTrials.gov Identifier: NCT03747601
• Recruitment Status: Unknown
• First Posted: November 20, 2018
• Last Update Posted: May 20, 2020
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborator: Boston University
• Information provided by (Responsible Party): Beth Israel Deaconess Medical Center

Tracking Information

• First Submitted Date: September 19, 2018
• First Posted Date: November 20, 2018
• Last Update Posted Date: May 20, 2020
• Actual Study Start Date: September 19, 2019
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 19, 2018)

• Humphrey visual field Mean Deviation (MD) [ Time Frame: Immediately after intervention ]
  Change in the mean deviation (PMD) Humphrey perimetry between baseline and post-stimulation
• Change in visual discrimination threshold [ Time Frame: Immediately after intervention ]
  Change in detection thresholds during stimulation compared to before stimulation.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Temporal Interference Brain Stimulation
• Official Title: The Development and Human Translation of Temporal Interference Brain Stimulation

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Device Feasibility
• Condition: Visual Acuity

Intervention

Device: Temporal Interference (TI) Stimulation

2-4 Temporal Interference stimulation sessions. The device is an experimental non-invasive electrical brain stimulator that functions similar to existing non-significant risk devices for electrical stimulation, including human non-invasive brain stimulation. Briefly, the device produces alternating current electrical stimulation in a kilohertz (kHz) range and results in less net charge applied within the brain. The device is powered by rechargeable 20 volt (V) battery (i.e. there is no connection to building power supply). The current is hardwired and limited to 5 milliamp (mA) via internal resistors. It includes extra safety features such as onboard fuses to limit any abrupt high current, and an emergency stop button which effectively insulates the subject and resets the device. The device was tested and characterized at all the required load conditions.

Study Arms

Experimental: Temporal Interference (TI) Stimulation

Temporal Interference stimulation applied to the head via standard electrodes

Intervention: Device: Temporal Interference (TI) Stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 19, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03747601
• Other Study ID Numbers: 2018P000603
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Beth Israel Deaconess Medical Center
• Original Responsible Party: Alvaro Pascual-Leone, MD, PhD, Beth Israel Deaconess Medical Center, Chief, Division of Cognitive Neurology
• Current Study Sponsor: Beth Israel Deaconess Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Boston University
• Investigators: Not Provided
• PRS Account: Beth Israel Deaconess Medical Center
• Verification Date: May 2020