Bipolar Transcranial Alternating Current Stimulation (tACS)

• ClinicalTrials.gov Identifier: NCT05480124
• Recruitment Status: Not yet recruiting
• First Posted: July 29, 2022
• Last Update Posted: January 19, 2023
• Sponsor: University of Michigan
• Collaborators: Milken Institute; Baszucki Brain Research Fund
• Information provided by (Responsible Party): Stephan F. Taylor, University of Michigan

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder	Device: tACS brain stimulation treatment; Device: Sham stimulation treatment	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Participants, study coordinator, and clinical assessor will be blind as to which session the participants receive active or sham treatment.
• Primary Purpose: Treatment
• Official Title: Enhancing Neural Synchrony and Affective Cognitive Control in Bipolar Disorder Using Personalized Transcranial Alternating Current Stimulation (tACS)
• Estimated Study Start Date: February 2023
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Sham Comparator: Sham stimulation treatment; Sham stimulation during a computerized task and electroencephalogram (EEG) recording.	Device: Sham stimulation treatment; 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.
Experimental: tACS brain stimulation treatment; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Severity of side effects reported at end of stimulation session as reported by the participant on the Stimulation Side Effects Questionnaire. [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) ]
   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.
2. Percentage of participants that withdrawal during or after the stimulation session [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) ]
   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.
3. Accuracy signal detection theory metric sensitivity (d') derived from the behavioral responses to Go and NoGo trials on the cognitive control task. [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and session 3 (approximately 60 minutes) ]
   D' (D prime) provides a measure of perceptual sensitivity to differing stimuli.
4. Accuracy signal detection theory metric response bias derived from the behavioral responses to Go and NoGo trials on the cognitive control task. [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) ]
   Beta (β) provides a measure of response bias, with negative β values indicating a stronger tendency to respond.
5. Reaction time (in milliseconds) of Go trials on the cognitive control task [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) ]
   The separate sessions will be measured separately and compared to each other.
6. Theta-gamma PAC (Kullback-Leibler Modulation Index) during the rest EEG blocks interleaved between stimulation blocks. [ Time Frame: Change in outcome between Session 2 (approximately 60 minutes) and 3 (approximately 60 minutes) ]
   Theta-Gamma PAC represents the relationship between the phase of theta oscillations and the amplitude of gamma oscillations as measured by the EEG.

Other Outcome Measures:

1. Emotional Flanker Task - Accuracy [ Time Frame: Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2) ]
   After completing the Emotion Go-NoGo task, participants will complete another cognitive control task (i.e., Emotional Flanker Task) with gray-scaled unpleasant, pleasant, and neural images from the International Affective Picture System. Participants are tasked with indicating which valance is presented in certain images while ignoring other images. Accuracy is defined as the percentage of trials that the participant correctly reports the valance of the target image. The total number of correct trials will be divided by the total number of trials to obtain an accuracy score. Average accuracy scores per condition and total will be calculated.
2. Emotional Flanker Task - Reaction time [ Time Frame: Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2). ]
   Reaction time will also be collected during the Emotional Flanker Task. Reaction time is defined as the length of time it takes the participant to respond after the onset of the stimuli. Average reaction times per condition and total will be calculated.
3. Emotional Flanker Task - EEG [ Time Frame: Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2). ]
   EEG will also be collected during the Emotional Flanker Task. Phase-amplitude coupling will be calculated and defined as the coupling between the amplitude of high frequency oscillations (e.g., gamma) and low frequency phase (e.g., theta). Average coupling scores per condition and total will be calculated.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 1.5 standard deviations (SDs) above published norms on the total score of the Barratt Impulsiveness Scale 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.

Contacts and Locations

Contacts

Contact: Laura Locarno; 734-232-4585; tacs_study@med.umich.edu

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Contact: Laura Stchur, MSW 734-936-1323 lmarine@med.umich.edu

Principal Investigator: Ivy Tso, PhD

Sponsors and Collaborators

University of Michigan

Milken Institute

Baszucki Brain Research Fund

Investigators

• Principal Investigator: Stephan F Taylor, MD; University of Michigan

More Information

• Responsible Party: Stephan F. Taylor, Professor of Psychiatry, University of Michigan
• ClinicalTrials.gov Identifier: NCT05480124
• Other Study ID Numbers: HUM00208557
• First Posted: July 29, 2022
• Last Update Posted: January 19, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Stephan F. Taylor, University of Michigan:

transcranial alternating current stimulation (tACS); electroencephalogram (EEG)

Additional relevant MeSH terms:

Bipolar Disorder; Bipolar and Related Disorders; Mental Disorders