Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Cue Reactivity as Assessed by the Attention Bias (AB) Task
研究概览
简要总结
The purpose of this study is to determine the effectiveness of a medication called suvorexant in reducing anxiety, improving sleep, and reducing cocaine cravings or cocaine use.
详细描述
Preclinical research has established important functions for the orexin system in mediating arousal/sleep, stress, and cue-induced reinstatement of drug taking (e.g., relapse). The role of stress/anxiety and drug cue reactivity in human drug relapse is well established, but to date, the role of the orexin system in modulating these phenomena has not been examined in humans with substance use disorders (e.g., cocaine). The goal of the present first-in-human study will be to examine the effects of an orexin antagonist (suvorexant) on interactions among stress/anxiety, sleep, and drug-cue reactivity. The study will utilize a battery of highly sensitive, drug-specific, laboratory measures of drug cue reactivity (a relapse risk model), and well-established metrics of stress/anxiety and sleep. The hypothesis is that antagonism of the orexin system will attenuate the link between (1) stress/anxiety and drug cue reactivity, and (2) sleep and drug cue reactivity. These results will elucidate a unique biochemical mechanism for understanding relapse, and provide a potential medication target for relapse prevention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •meet current DSM-5 criteria for cocaine use disorder (CUD) of at least moderate severity (≥4 symptoms)
排除标准
- •current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, or nicotine
- •have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe
- •significant current suicidal or homicidal ideation
- •medical conditions contraindicating administration of suvorexant (e.g., severe pulmonary disease, severe cardiovascular disease or clinically abnormal EEG, severe liver or kidney disease, seizure disorder, or sleep disorder - particularly narcolepsy)
- •taking medications known to have significant drug interactions with the study medication(s) (e.g., MAO inhibitors, anticonvulsants, haloperidol, phenothiazines, anesthetics, and all sedatives)
- •currently or recently (last 3 months) treated for substance use [other than cocaine or nicotine] or another psychiatric condition
- •conditions of probation or parole requiring reports of drug use to officers of the court; (8) impending incarceration
- •pregnant or nursing for female patients
- •inability to read, write, or speak English [required for lab tasks and psychometric scales]
- •unwillingness to sign a written informed consent form
- •subjects with alcohol use disorders or are drinking > 7 alcoholic drinks per week. All subjects who are excluded will be given referral information to other local treatment programs.
研究组 & 干预措施
suvorexant
Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM.
干预措施: suvorexant (Drug)
Placebo
Subjects will receive placebo once daily at 10 PM.
干预措施: Placebo (for suvorexant) (Drug)
结局指标
主要结局
Cue Reactivity as Assessed by the Attention Bias (AB) Task
时间窗: day 14
The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale.
时间窗: day 0
DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Total Sleep as Assessed by the Misfit Shine Device
时间窗: day 14
Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
时间窗: day 14
DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
时间窗: day 11
DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Anxiety as Assessed by the DASS21 Self-report Questionnaire
时间窗: day 14
DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
次要结局
- Stress as Assessed by a Visual Analog Scale (VAS) for Stress(day 0, day 2, day 4, day 7, day 9, day 11, and day 14)
- Percent Medication Compliance as Assessed by Pill Counts(day 2, day 4, day 7, day 9, day 11, and day 14)
- Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples(day 2, day 4, day 7, day 9, day 11, and day 14)
- Percent Medication Compliance as Assessed by Text Reminders and Replies(day 2, day 4, day 7, day 9, day 11, and day 14)
- Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI)(day 0, day 2, day 4, day 7, day 9, day 11, and day 14)
- Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure(day 0, day 7, and day 14)
- Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief(day 0, day 7, and day 14)
- Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure(day 0, day 7, and day 14)
- Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT)(day 0, day 7, and day 14)
- Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles(day 2, day 4, day 7, day 9, day 11, and day 14)
研究者
Scott Lane
Professor
The University of Texas Health Science Center, Houston