Bipolar Transcranial Alternating Current Stimulation (tACS)

Study Overview
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Brief Summary
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The purpose of this clinical trial is to measure the safety and effectiveness of a non-invasive brain stimulation device called Transcranial Alternating Current Stimulation (tACS) in participants with bipolar disorder (BD). Participants will be asked to come in for 3 sessions. If participants qualify at the screening visit (session 1) then enrolled participants will complete sessions 2 and 3 as well as have a 30-day follow-up phone call.

Official Title
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Enhancing Neural Synchrony and Affective Cognitive Control in Bipolar Disorder Using Personalized Transcranial Alternating Current Stimulation (tACS)

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Device: tACS brain stimulation treatment
* Device: Sham stimulation treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of BD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria being met from previous enrollment in the Prechter Bipolar Longitudinal Study This study will select BD patients that scored above published norms (upper 50th percentile) on the NEO-PI impulsivity facet to ensure that the recruited patients exhibit the network dysfunction targeted by the tACS paradigm and therefore have the potential to benefit from this neuromodulation technique. Patients must be on a stable dose of medication for two weeks prior to Sessions 2 and 3. Exclusion Criteria: Significant neurological abnormalities, such as seizure disorder, mass lesions, etc. Known Mendelian disorder Active problematic substance use in the past 30 days (as determined by the Substance Use Disorder module of SCID) Evidence of suicidal intentions or behaviors in the past month, as judged by affirmative responses to question number 4 or number 5 on the Columbia Suicide Severity Rating Scale (CSSRS) or report of suicidal behaviors in the last 6 months Pregnant or trying to become pregnant, or currently lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham stimulation treatment<br>Sham stimulation during a computerized task and electroencephalogram (EEG) recording. | Device: Sham stimulation treatment<br>* Participants will wear an EEG cap on the head attached with EEG-recording and tACS electrodes. Sham tACS will be delivered by passing a transient (approximately 12 seconds ) small electrical current via the tACS electrodes during a computerized behavioral task. The effect of sham stimulation on EEG will be measured via EEG-recording electrodes during short rests (between stimulation blocks). The sham stimulation session will last for approximately 60 minutes. After treatment, participants will be asked about the experience and if there are any side effects.<br>|
| Experimental: tACS brain stimulation treatment<br>tACS brain stimulation during a computerized task and EEG recording. Participants will receive tACS using individualized peak Phase-amplitude coupling (PAC) frequency pairs determined in Session 1. | Device: tACS brain stimulation treatment<br>* Participants will wear an EEG cap on the head attached with EEG-recording and tACS electrodes. tACS will be delivered by passing a small electrical current via the tACS electrodes to the scalp to stimulate brain activity during a computerized behavioral task. The effect of active stimulation on EEG will be measured via EEG-recording electrodes during short rests (between stimulation blocks). The stimulation session will last for approximately 60 minutes. After treatment, participants will be asked about the experience and if there are any side effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of side effects reported at end of stimulation session as reported by the participant on the Stimulation Side Effects Questionnaire. | The score is calculated by summing the severity score of items (0-4) that are rated by the participant as related to stimulation (ratings of 3=probable or 4=definite) on the Stimulation Side Effects Questionnaire. There are a total of 14 symptoms as well as an other category with scores ranging from 0-56 and the possibility of more points if other symptoms are recorded. | Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) | 
| Percentage of participants that withdrawal during or after the stimulation session | The study team will compare the percentage of participants requesting to discontinue the session and the severity of side effects reported following the tACS vs. sham procedure. | Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) | 
| Accuracy signal detection theory metric sensitivity (d') derived from the behavioral responses to Go and NoGo trials on the cognitive control task. | D' (D prime) provides a measure of perceptual sensitivity to differing stimuli. | Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) | 
| Accuracy signal detection theory metric response bias derived from the behavioral responses to Go and NoGo trials on the cognitive control task. | Beta (β) provides a measure of response bias, with negative β values indicating a stronger tendency to respond. | Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) | 
| Reaction time (in milliseconds) of Go trials on the cognitive control task | The separate sessions will be measured separately and compared to each other. | Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) | 
| Theta-gamma PAC (Kullback-Leibler Modulation Index) during the rest EEG blocks interleaved between stimulation blocks. | Theta-Gamma PAC represents the relationship between the phase of theta oscillations and the amplitude of gamma oscillations as measured by the EEG. | Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial alternating current stimulation (tACS), electroencephalogram (EEG)