Using Repetitive Transcranial Magnetic Stimulation (rTMS) to Explore Neural Mechanisms of Stress-Induced Opioid Use
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Digit Span Task
研究概览
简要总结
This study will use a stress (vs. placebo) exposure model, paired with single-session sham vs. active rTMS at two distinct cortical locations (dlPFC vs. mPFC in parallel groups) to assess whether rTMS neuromodulation at these alternative loci differentially influence stress-reactivity and opioid reinforcement in non-treatment seeking participants with OUD. Stress-reactivity will be measured using cognitive, affective, behavioral and biological phenotypes.
详细描述
The Competing Neurobehavioral Decisions Systems (CNDS) model of addiction suggests that persons with SUDs have hyperactive limbic reward circuitry and hypoactive executive control circuitry. CNDS theory supports targeting the dorsolateral prefrontal cortex (dlPFC, part of executive control circuit) and other cortical targets with repetitive transcranial magnetic stimulation (rTMS). One candidate-the medial prefrontal cortex (mPFC)-is part of limbic reward circuitry and accessible using rTMS. We validated a rigorous pharmacological stress-induction method (yohimbine + hydrocortisone) that emulates endogenous stress-reactivity and have established linkages between stress-exposure, executive dysfunction, and drug seeking. Our lab is developing rTMS as a potential "anti-stress" neuromodulation approach in people with opioid use disorder (OUD).
This study will use a stress (vs. placebo) exposure model, paired with single-session sham vs. active rTMS at two distinct cortical locations (dlPFC vs. mPFC in parallel groups) to assess whether rTMS neuromodulation at these alternative cortical loci differentially influence stress-reactivity and opioid reinforcement in non-treatment seeking participants with OUD. Stress-reactivity will be measured using cognitive, affective, behavioral and biological phenotypes.
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
placebo for stressor, and sham figure of 8 coil for rTMS
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet DSM-5 criteria for OUD
- •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 within ranges for safe use of the pharmacological 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 other than opioids (except marijuana, which is legal in Michigan)
- •Urinalysis positive for cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy
- •Medical conditions prohibiting use of rTMS (e.g. seizure history; based on rTMS screening questionnaire)
- •Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, or obsessive compulsive disorder; major depression in the past 5 years; or potentially antisocial personality disorder (if the clinical psychologist judges such behaviors to be potentially disruptive or unsafe in our lab)
- •Past-year SUD other than OUD
- •Acute/unstable illness: 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
- •Past-month participation in a research study
研究组 & 干预措施
placebo stressor, sham rTMS
placebo stressor (lactose), sham rTMS (inactive coil)
干预措施: sham rTMS (Device)
placebo stressor, sham rTMS
placebo stressor (lactose), sham rTMS (inactive coil)
干预措施: Placebo oral tablet (Drug)
placebo stressor, active rTMS
placebo stressor (lactose), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)
干预措施: Placebo oral tablet (Drug)
placebo stressor, active rTMS
placebo stressor (lactose), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)
干预措施: active rTMS (Device)
stressor, sham rTMS
stressor (yohimbine 54mg + hydrocortisone 20mg), sham rTMS (inactive coil)
干预措施: Yohimbine + Hydrocortisone (Drug)
stressor, sham rTMS
stressor (yohimbine 54mg + hydrocortisone 20mg), sham rTMS (inactive coil)
干预措施: sham rTMS (Device)
stressor, active rTMS
stressor (yohimbine 54mg + hydrocortisone 20mg), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)
干预措施: Yohimbine + Hydrocortisone (Drug)
stressor, active rTMS
stressor (yohimbine 54mg + hydrocortisone 20mg), active rTMS (10 Hz dlPFC in group 1; 1 Hz mPFC in group 2)
干预措施: active rTMS (Device)
结局指标
主要结局
Digit Span Task
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
number of digits recalled, measure of verbal working memory
Blood pressure
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Systolic/diastolic BP (mm Hg)
Saliva alpha-amylase level
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Saliva alpha-amylase level (U/mL)
Desire for Drug Questionnaire
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
opioid craving score
Addiction Stroop task
时间窗: change from pre- and post-intervention in each of 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- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
number of correct items, measures ability to shift set and assesses cognitive flexibility
Monetary Incentive Delay task
时间窗: change from pre- and post-intervention in each of 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- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
rate of monetary discounting
Drug/Money Choice Task
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
number of hypothetical choices between a constant amount of preferred opioid (relative to money)
Heart rate
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Heart rate (beats/min)
Saliva cortisol level
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Saliva cortisol level (µg/dL)
Serum prolactin level
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Serum prolactin level (pg/dL)
Serum BDNF level
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
Serum brain derived neurotrophic factor level (pg/dL)
Positive and Negative Affect Schedule (PANAS) positive affect
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
10-item sub scale score of positive affect
Positive and Negative Affect Schedule (PANAS) negative affect
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
10-item sub scale score of negative affect
State Trait Anxiety Inventory
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
state anxiety scores
Opiate-32 Questionnaire, Agonist score
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
total opioid agonist score (16 items)
Opiate-32 Questionnaire, Withdrawal score
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
total opioid withdrawal symptom score (16 items)
Resting-state EEG activation
时间窗: change from pre- and post-intervention in each of 4 sessions (through study completion, about 1 month total)
relative (gamma band ÷ slow band) ratio in electroencephalogram (EEG) power during resting state
次要结局
未报告次要终点
研究者
Mark Greenwald, PhD
Professor
Wayne State University