Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Color-Word Stroop Task
研究概览
简要总结
This preliminary study is designed to evaluate mechanisms by which excitatory dorsolateral prefrontal cortex (dlPFC) repetitive transcranial magnetic stimulation (rTMS) (vs. sham) and pharmacological stress (vs. placebo) alter behavior in non-treatment seeking individuals with opioid use disorder (OUD). Specific Aims are to (1) Evaluate how stress impacts domains of behavior including (1a) executive function and (1b) opioid-seeking behavior; and (2) Determine whether rTMS stimulation attenuates (2a) executive dysfunction, (2b) stress-reactivity, and (2c) opioid-seeking in individuals with OUD not receiving treatment.
详细描述
This study will use a double-blind, 10Hz left dlPFC rTMS (vs. sham) and pharmacological stressor ([yohimbine + hydrocortisone] vs. placebo) within-subject, randomized crossover design. Each participant will complete 4 sessions (stressor vs. placebo, crossed with rTMS vs. sham), each separated by at least 1 week. Participants will complete these 4 (2x2 within subject) test conditions in randomized order: sham rTMS/placebo stress, sham rTMS/active stress, active rTMS/ placebo stress, and active rTMS/active stress.
The PI will perform randomization using a Latin Square and will assign participants to conditions and prepare medication (stressor or placebo) for each participant's sessions. The PI will keep others blinded and will not be involved in study assessments.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Placebo (lactose) for pharmacological stressor, and sham for dlPFC 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; and
- •Past-month participation in a research study.
研究组 & 干预措施
placebo stressor, sham rTMS
Placebo stressor (lactose) + sham (inactive) rTMS over the left dlPFC
干预措施: Placebo (Drug)
placebo stressor, sham rTMS
Placebo stressor (lactose) + sham (inactive) rTMS over the left dlPFC
干预措施: Sham rTMS (Device)
placebo stressor, active rTMS
Placebo stressor (lactose) + active 10Hz rTMS over the left dlPFC
干预措施: Active rTMS (Device)
placebo stressor, active rTMS
Placebo stressor (lactose) + active 10Hz rTMS over the left dlPFC
干预措施: Placebo (Drug)
active stressor, sham rTMS
Stressor (yohimbine 54mg + hydrocortisone 20mg) + sham (inactive) rTMS over the left dlPFC
干预措施: Yohimbine + Hydrocortisone (Drug)
active stressor, sham rTMS
Stressor (yohimbine 54mg + hydrocortisone 20mg) + sham (inactive) rTMS over the left dlPFC
干预措施: Sham rTMS (Device)
active stressor, active rTMS
Stressor (yohimbine 54mg + hydrocortisone 20mg) + active 10Hz rTMS over the left dlPFC
干预措施: Yohimbine + Hydrocortisone (Drug)
active stressor, active rTMS
Stressor (yohimbine 54mg + hydrocortisone 20mg) + active 10Hz rTMS over the left dlPFC
干预措施: Active rTMS (Device)
结局指标
主要结局
Color-Word Stroop Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measures cognitive control in response to opioid-related words.
Digit Span Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measures verbal working memory. Participants are asked to repeat strings of numbers of increasing length, both forward and backward.
Positive and Negative Affect Schedule
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
subjects rate their positive and negative affect
State-Trait Anxiety Inventory
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
subjects rate their level state anxiety
Diastolic blood pressure
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
millimeters mercury (mmHg)
Saliva cortisol level
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measure of the activity of the HPA axis
Relative electroencephalogram (EEG) gamma power
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Prefrontal gamma (25-100 Hz) EEG power, relative to slow-wave EEG power, is a stress biomarker
Drug/Money Choice Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
participants choose hypothetically between a constant amount of their preferred opioid ($10 unit dose) or money ($2)
Systolic blood pressure
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
millimeters mercury (mmHg)
Heart rate
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
beats per minute
Wisconsin Card Sorting Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
measures ability to shift set and assesses cognitive flexibility.
Saliva alpha-amylase level
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
indirect measure of adrenergic stimulation
Serum brain derived neurotrophic factor (BDNF) level
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
indirect measure of brain derived neurotrophic factor activation
Emotion Regulation Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
subjects rate the unpleasantness and arousal of different emotional pictures
Monetary Incentive Delay Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Participants respond to a visual target that follows 2 different cues: incentive or non-incentive. No reward or punishment occurs on non-incentive trials. On incentive trials, participants must respond within a fixed amount of time. In the reward condition, responses within that time result in receiving the incentive , else nothing. In the punishment condition, the participant will lose money if they do not respond within the time limit
Delay Discounting Task
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
Participants perform a brief (\<1min) hypothetical version of the traditional monetary task with a 5-trial adjusting delay previously validated to rapidly assess discount rate
Serum prolactin level
时间窗: change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total)
indirect measure of dopamine stimulation
次要结局
- Opioid craving(change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total))
- Opioid withdrawal symptoms(change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total))
- Opioid agonist symptoms(change from pre- to post-intervention in each of 4 sessions (through study completion, about 1 month total))
研究者
Mark Greenwald, PhD
Principal Investigator
Wayne State University