Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) of Limbic Brain Circuitry in Stress Modulation in a Healthy Population
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Monetary Incentive Delay Task
研究概览
简要总结
This study will be conducted with healthy male and female participants. Aim 1 will determine during sham repetitive transcranial magnetic stimulation (rTMS) how a drug stressor combination (yohimbine + hydrocortisone) relative to placebo alters : (1a) impulsivity; (1b) mood; and (1c) physiology. Aim 2 will determine whether active rTMS over the medial prefrontal cortex alters the effects of stress-exposure on (2a) decision-making, (2b) mood, and (2c) biomarkers of stress.
详细描述
This study will use a double-blind, within-subjects randomized crossover design. Each participant will complete 4 sessions in this two-factor (2x2) combinatorial design: 1Hz medial prefrontal cortex (mPFC) vs. sham repetitive transcranial magnetic stimulation (rTMS) X pharmacological stressor (yohimbine 54mg + hydrocortisone 20mg) vs. placebo, with each session separated by at least 1 week. Participants will be asked not to use alcohol or drugs for 24-hr before arriving at the lab. We expect to complete screen at least 20 individuals to complete 12 individuals in this study. Candidates will first undergo psychiatric and medical screening to rule out contraindications to participation. Once enrolled, each participant will complete, in randomized order, the 4 conditions above. Periodic measures will be collected before and after the rTMS/sham and stress/placebo interventions. These measures will include subjective, behavioral and physiological assessments, as well as saliva and blood samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
sham (inactive) figure of 8 coil for rTMS, and placebo for pharmacological stressor
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 21-60 yr
- •Right-handed
- •Males and non-pregnant/non-lactating females
- •Cognitively intact (total IQ score >80 on Shipley Institute of Living Scale)
- •Screening cardiovascular indices must be within ranges that allow for safe use of stressor: resting HR 50-90 bpm, systolic BP 90-140 mmHg, and diastolic BP 50-90 mmHg
- •Use alcohol and/or marijuana <3 times/week; each "time" should consist of <1 marijuana "joint" equivalent and <3 alcoholic drinks
排除标准
- •Under influence of any substance during session
- •Past 7-day use of illicit drugs (excluding marijuana) based on Timeline Followback interview
- •Urine positive for opioids, cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy
- •Medical conditions prohibiting use of rTMS (e.g. seizure history; using validated rTMS screening instrument)
- •Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, or major depression that is not substance-induced
- •Past-year substance use disorder
- •Medical conditions making it unsafe for participation (e.g. neurological, cardiovascular, pulmonary, or systemic diseases)
- •Lactose intolerance (placebo dose)
- •Any prohibited medications: medications that lower seizure threshold, psychiatric medications, prescription pain medications, or blood pressure medications
- •Chronic head or neck pain
- •Taken part in any research studies in the past month
研究组 & 干预措施
active stress, active rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
干预措施: yohimbine + hydrocortisone (Drug)
placebo stressor, sham rTMS
placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil
干预措施: Placebo oral tablet (Drug)
placebo stressor, sham rTMS
placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil
干预措施: sham rTMS (Device)
placebo stressor, active rTMS
placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
干预措施: medial prefrontal cortex rTMS (Device)
placebo stressor, active rTMS
placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
干预措施: Placebo oral tablet (Drug)
active stress, sham rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil
干预措施: yohimbine + hydrocortisone (Drug)
active stress, sham rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil
干预措施: sham rTMS (Device)
active stress, active rTMS
active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
干预措施: medial prefrontal cortex rTMS (Device)
结局指标
主要结局
Monetary Incentive Delay Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of rewards received, measure of motivation
Delay Discounting Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
rate of monetary discounting
Color-Word Stroop Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
reaction time (msec) measure of cognitive interference
Wisconsin Card Sorting Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of correct items, measure of ability to shift set and assesses cognitive flexibility
Digit Span Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of digits recalled, measure of verbal working memory
State-Trait Anxiety Inventory
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
questionnaire subscale that measures state anxiety
Effort Choice Task
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
number of progressive ratio (PR) choices vs. fixed ratio (FR) choices
Positive and Negative Affect Schedule (PANAS) positive affect
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
10-item questionnaire sub scale that measures positive affect
Positive and Negative Affect Schedule (PANAS) negative affect
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
10-item questionnaire sub scale that measures negative affect
Blood pressure
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Blood pressure (mm Hg)
Heart rate
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Heart rate (beats/min)
Plasma BDNF level
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma brain derived neurotrophic factor level (pg/mL)
Saliva cortisol level
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva cortisol level (µg/mL)
Saliva alpha-amylase level
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Saliva alpha-amylase level (U/mL)
Plasma prolactin level
时间窗: change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total)
Plasma prolactin level (pg/mL)
次要结局
未报告次要终点
研究者
Mark Greenwald, PhD
Professor
Wayne State University