Targeted Alternating Current and Cognitive Training Intervention for Cognitive Control in Bipolar Disorders (TACTIC-BD)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Affective Go/NoGo task
研究概览
简要总结
This study is testing whether a type of gentle brain stimulation, combined with computer-based brain training exercises, can help improve thinking skills in Veterans with bipolar disorder. Veterans with bipolar disorder may have difficulty with skills like stopping to think before acting or adjusting their behavior when things change - problems that can affect daily life and have been linked to a higher risk of serious outcomes.
In this study, Veterans with bipolar disorder will complete brain training exercises at home on a computer, paired with a mild electrical brain stimulation called transcranial alternating current stimulation (tACS), delivered through a small headband worn on the forehead. Some participants will receive real stimulation and some will receive an inactive ("sham") version, and neither participants nor most study staff will know which one a person is receiving. All participants will also complete brain wave recordings (EEG), interviews, questionnaires, and various thinking tasks before and after the study to measure any changes. A separate group of Veterans without bipolar disorder will complete the same tests, without any brain stimulation or training, to help researchers understand how much change would happen naturally just from taking the same tests more than once.
The goal of this research is to learn whether this combined treatment approach is safe, tolerable, and helpful for improving thinking skills in Veterans with bipolar disorder, and whether Veterans find it an acceptable treatment worth continuing.
详细描述
Veterans with bipolar disorder (BD) are at elevated risk for suicide, recurrent homelessness, and disability, and existing pharmacological and psychosocial treatments show limited efficacy for the cognitive dysfunction that underlies these outcomes. Cognitive control (CC) - encompassing response inhibition, error monitoring, and adaptive responding to changing contingencies - is a core, trait-like neurocognitive deficit in BD that persists across mood states (mania, depression, euthymia) and is mechanistically linked to symptom severity and suicidality. No prior studies have examined neuromodulation targeting CC processes in Veterans with BD.
This study is a randomized, double-blind, sham-controlled trial testing whether transcranial alternating current stimulation (tACS) targeting frontal theta oscillations, delivered concurrently with CC-relevant cognitive training, improves neural and behavioral indices of CC beyond cognitive training alone. Ninety-two Veterans with a DSM-5 diagnosis of Bipolar I, Bipolar II, or Other Specified Bipolar Disorder will complete a baseline assessment battery, including self-report measures, EEG (resting-state and task-based), and behavioral paradigms indexing CC in both affective and non-affective contexts (e.g., Go/NoGo, Dot Pattern Expectancy, Monetary Incentive Delay tasks). Participants will then be randomized 1:1 to 10 sessions of active (5Hz, 1mA) or sham frontal theta-frequency tACS (electrodes at F3/F4), each paired with concurrent computerized cognitive training (BrainHQ) targeting working memory, inhibitory control, set-shifting, and attention. All intervention sessions will be self-administered in participants' homes under real-time remote supervision via videoconference. Follow-up assessments repeating the baseline CC battery will occur at approximately 1-week and 2-months post-intervention.
An additional 46 Veterans without major psychopathology will complete an identical assessment schedule (baseline and two follow-up visits) without any intervention, in order to establish practice-effect benchmarks independent of neuromodulation, cognitive training, or mood symptomatology - a design feature intended to isolate true intervention effects from repeated-testing effects, consistent with methodological recommendations for cognitive intervention trials in serious mental illness.
Primary outcomes include change over time in behavioral (d' on Affective and non-affective Go/NoGo and Dot Pattern Expectancy tasks; Trail Making Test-B completion time) and EEG (frontal theta amplitude during the Monetary Incentive Delay task; error-related positivity during the Go/NoGo task) indices of CC, comparing active versus sham tACS groups relative to the practice-effect benchmark established by the control cohort. Secondary outcomes include self-report CC measures (UPPS-P, MPQ-BF Control subscale), qualitative acceptability data from semi-structured exit interviews with the BD cohort, and cross-sectional associations between baseline CC indices and lifetime severity of (hypo)mania, depression, and suicidality. Exploratory analyses will examine intervention effects on general cognitive functioning and the influence of subthreshold mood symptoms on treatment response.
This study is the first to test remotely delivered tACS combined with cognitive training in Veterans with BD, and is designed to establish feasibility, acceptability, and preliminary efficacy data to inform future trials examining long-term effects on BD illness course, including suicidality and functional outcomes.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 三盲 (受试者、研究者、结局评估者)
盲法说明
This study uses double-blind masking for the randomized comparison between active and sham tACS. Participants with bipolar disorder, study staff administering the intervention and conducting outcome assessments, and study investigators are all unaware of treatment assignment (active vs. sham), as both conditions use identical electrode setup, session structure, and device programming delivered via participant- and session-specific activation codes. An unblinded biostatistician and/or device programmer, who are not involved in participant assessment or clinical decision-making, will maintain the randomization key and generate the activation codes to preserve blinding among all other study personnel. Blinding integrity will be assessed at the end of the intervention period using a blinding questionnaire. The control cohort (Veterans without major psychopathology) is not blinded, as this group does not receive randomized intervention assignment.
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- Veteran
- Capacity to provide voluntary informed consent
- English language fluency
- Stable dose of prescription and non-prescription medications that may impact cognition for at least 3 weeks prior to consent
- Bipolar Disorder (BD) cohort only: A primary diagnosis of Bipolar I Disorder, Bipolar II Disorder, or Other Specified Bipolar Disorder (i.e., those with major depressive episodes and hypomania that meet all episode criteria but for duration)
排除标准
- Presence of a medical, psychiatric, physical or non-physical disease, disorder, condition, injury, disability or pre-existent history such that study participation, in the opinion of the study investigators: a) May pose a significant risk to the participant, b) raises the possibility that the participant is unlikely to successfully complete all the requirements of the study according to the study protocol, or c) might adversely impact the integrity of the data or the validity of the study results. Specific conditions may include (but are not limited to) a history of brain tumor near the stimulation site, brain surgery, severe traumatic brain injury (TBI) (LOC >24 hours, GCS 3-8), stroke with current sequalae, epilepsy, Multiple Sclerosis, Huntington's Disease, ALS, ataxia, aphasia, Alzheimer's Disease, dementia, cardiac pacemaker or defibrillator, blindness, or deafness.
- Bipolar Disorder (BD) cohort only: a) Current/acute episode criteria met for any Bipolar Disorder (BD) episode (i.e., hypomania, mania, depression) for the month prior to consent as assessed by SCID-5-RV's Module A, b) Current/acute substance use disorder with severe specifier and/or evidence of withdrawal or increased tolerance, as assessed by SCID-5-RV's Module E, c) Contraindications for transcranial alternating current stimulation (tACS), e.g., metallic cranial or facial implant, dermatologic conditions on the forehead, etc. d) No or limited internet connection in their home
- Control cohort only: a) Current or lifetime bipolar disorders or symptoms of psychosis assessed by SCID-5-RV, and/or b) Clinically significant mental health disorders within 2 years of consent (e.g., major depressive disorder, generalized anxiety disorder, post-traumatic stress disorder, substance use disorder as specified in 2b) as assessed by SCID-5-RV
- Court-appointed legal guardianship
- Cognitive training or neuromodulation treatments for clinical or research purposes within 30 days of consent or during study period (consent to final follow-up)
- Electroconvulsive Therapy (ECT) within 12 months of consent or during study period
- Baseline MoCA score <18 or MoCA-Blind score <19
- Baseline acute severe suicidal ideation as determined by a score > 3 on the Depressive Symptom Index-Suicidality Subscale (DSI-SS)
- Positive pregnancy screen in participants of childbearing potential
研究组 & 干预措施
Active transcranial alternating current stimulation (tACS)+ Cognitive Training
Veterans with bipolar disorder randomized to this arm receive 10 sessions of active frontal theta-frequency transcranial alternating current stimulation (tACS; 5Hz, 1mA, delivered via electrodes at F3/F4), administered concurrently with computerized cognitive training (BrainHQ) targeting working memory, inhibitory control, set-shifting, and attention. Sessions are self-administered at home under real-time remote supervision.
干预措施: Soterix 1x1 tES mini-CT (Device)
Sham transcranial alternating current stimulation (tACS)+ Cognitive Training
Veterans with bipolar disorder randomized to this arm receive 10 sessions of sham (inactive) tACS, using identical electrode placement, session structure, and setup as the active arm, but without sustained active current delivery beyond a brief onset sensation. This arm receives the same concurrent cognitive training (BrainHQ) as the active arm, allowing isolation of tACS-specific effects beyond cognitive training alone.
干预措施: Soterix 1x1 tES mini-CT (Device)
Control (No Intervention)
Veterans without major psychopathology complete the same baseline and follow-up assessment schedule (self-report, behavioral, and EEG measures of cognitive control) as the BD cohort, without receiving cognitive training, tACS, or sham tACS. This arm establishes practice-effect benchmarks to distinguish true intervention effects from repeated-testing effects. This arm is assigned by eligibility status, not randomization.
结局指标
主要结局
Affective Go/NoGo task
时间窗: Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up
The Affective Go/NoGo task assesses response inhibition within an emotionally salient context, in contrast to purely non-affective measures of cognitive control. On each trial, a word with positive, negative, or neutral emotional valence is presented at the center of the screen; participants are instructed to respond as quickly as possible to target words of a designated valence (e.g., positive) while withholding responses to distractor words of the other two valences (e.g., negative or neutral). This design requires participants to inhibit prepotent responses to emotionally salient but task-irrelevant stimuli, capturing the interaction between affective processing and cognitive control. Affective response inhibition will be indexed by overall task accuracy using d', consistent with signal detection approaches to response inhibition performance.
Dot Pattern Expectancy (DPX) task
时间窗: Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up
The Dot Pattern Expectancy (DPX) is a dot-based variant of the AX-Continuous Performance Test (AX-CPT) used to assess cognitive control in the context of proactive response preparation and contextual updating. On each trial, participants are presented with a cue (white) followed by a probe (light blue), separated by a 2500-3500 ms interval; a target response is required only when a valid cue ("A") is followed by a valid probe ("X"), yielding four trial types: AX (target), AY, BX, and BY (nontarget). The outcome measure is overall task accuracy, calculated using the discriminability index (d'), a signal detection measure calculated as the z-transformed hit rate minus the z-transformed false alarm rate, adjusted for performance. The d' score is a continuous measure with a range of -4 to 4; higher d' scores indicate better discrimination between target and non-target trials, reflecting stronger cognitive control.
Trail Making Test-B (TMT-B)
时间窗: Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up
The Trail Making Test-B (TMT-B) is a widely used, paper-and-pencil neuropsychological measure of cognitive flexibility and set-shifting. Participants are asked to draw a line connecting a series of numbered and lettered circles in alternating sequential order (e.g., 1-A-2-B-3-C), as quickly and accurately as possible. Because successful performance requires continuously shifting attention between two different response sets, TMT-B is considered a sensitive index of executive/cognitive control, with longer completion times reflecting greater difficulty in adaptive, flexible responding. The primary outcome measure is time to completion.
Go/NoGo task
时间窗: Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up
EEG will be recorded during a Go/NoGo task in which participants are instructed to respond via button press to any letter other than "X" (Go trials) and to withhold response when an "X" appears (NoGo trials), while responding as quickly as possible and minimizing errors. Participants complete two blocks totaling 228 trials, with approximately 24% designated as NoGo trials; letters are presented for 2000 ms with a randomized intertrial interval of 800-1200 ms. Because Go trials occur more frequently than NoGo trials, the task design induces a prepotent tendency to respond, increasing demand on inhibitory control during NoGo trials. Behavioral accuracy will be indexed by d'. The primary neural outcome of interest is the event-related potential (ERP) time-locked to the button-press response reflecting conscious error detection, indexed by error-related positivity (Pe) amplitude.
Monetary Incentive Delay (MID) task
时间窗: Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up
The Monetary Incentive Delay (MID) task assesses neural responses associated with anticipating and receiving monetary outcomes. Participants complete 180 trials across three blocks; each trial begins with a 250 ms cue indicating a potential gain, loss, or neutral outcome, denoted by line markings corresponding to magnitude ($0.25-$5.00). Following a 1,500 ms fixation period, a brief target (180-280 ms) appears, requiring a speeded button press to win or avoid losing money; target duration is adaptively titrated to maintain approximately 70% accuracy across participants. Trial outcome feedback is presented for 1,650 ms, followed by a 500 ms display of cumulative earnings, and participants are compensated with a portion of their total winnings at the conclusion of the task. EEG is recorded continuously throughout the task, with frontal theta power during the reward anticipation period serving as the primary neural outcome measure.
次要结局
- UPPS-P Impulsive Behavior Scale(Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up)
- MPQ-BF(Baseline (Week 0), Week 3 Follow-Up, Week 10 Follow-Up)
- Exit Interview(Week 10 Follow-Up)
研究者
研究点 (1)
标识符
- NCT 编号
- NCT07845409
- 其他研究编号
- MHBC-004-26S
日期
- 首次提交
- (21天前)
- 首次发布
- (前天)
- 主要完成日期
- (4年后)
- 研究完成日期
- (4年后)
- 最近核实
- (29天前)
- 最近更新
- (前天)
监管与共享
- FDA 监管药物
- 否
- FDA 监管器械
- 是
- 个体参与者数据共享计划
- 否
- 是否有结果
- 否