Biobehavioral Studies of Opioid Seeking: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Opioid price-inelasticity (economic demand)
研究概览
简要总结
This research deals with behaviors that are part of opioid dependence. The purpose is to study how stress and medication dose can affect opioid drug use.
详细描述
If participants meet all the criteria, their involvement in the study (Phases 1 and 2 described below) will last for 10-13 weeks. Participants will be asked to stay at the research site for a minimum of 2 nights on 4 separate weeks and will have 22 office visits During that time, participants can't leave the unit unescorted or have visitors.
Participants will receive a medication called Buprenorphine/Naloxone. Buprenorphine/Naloxone is approved by the Food and Drug Administration (FDA) to treat opioid addiction, and is a safe and effective alternative to methadone. Participants will receive this medication every day. When participants are not living on the inpatient unit they will come to the research clinic every day to receive the medication.
On Day 1, one single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect of the Buprenorphine/Naloxone medication dose on gene expression pattern.
On each day of admission (once on weeks 3, 5 and 7), a single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect of the buprenorphine/naloxone medication dose on the participant's gene expression pattern.
On the 8 days while participants are an inpatient they will participate in experimental sessions that involve drug administration. On some days participants will receive morphine and on some days participants will receive oral medications called yohimbine and hydrocortisone that will be used to study stress responses. Each afternoon study staff will collect one blood sample (10 mL or 2 teaspoons) from a vein in the participant's arm; these samples will be used to measure biological signals of stress.
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
Medication conditions blinded using different-sized buprenorphine/naloxone sublingual tablets including placebo. Stress conditions blinded using encapsulation of yohimbine/placebo and hydrocortisone/placebo. Only pharmacy aware of drug codes.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Opioid dependent, as determined by structured clinical interview for DSM-IV (SCID) and Addiction Severity Index (ASI)
- •Positive urine test for opiates
- •Willing to use an adequate form of contraception for the duration of the study.
- •Reads and writes English
- •Participants must be in generally good health to be eligible. All candidates will receive a routine medical exam (history and physical) with standard laboratory tests (including blood and urine samples, EKG, mandatory TB testing, and voluntary HIV testing).
排除标准
- •No candidate who has a current DSM-IV Axis I disorder other than Drug Dependence or a history of serious psychiatric problems (e.g. psychosis, bipolar or major depression) will be allowed to participate.
- •Candidates meeting criteria for opioid or nicotine dependence will not be excluded, but those with other Substance Dependence disorders will be excluded. Those with Abuse of Alcohol, Cannabis, Cocaine, will not be excluded, but participants must provide an alcohol free breath specimen.
- •No candidate with medical (neurological, cardiovascular, pulmonary or systemic) disorders will be allowed to participate. This will be determined with history and physical exam, standard laboratory testing (blood and urine), EKG, and TB tests (to avoid transmitting this communicable disease on the residential unit or in the laboratory).
- •Candidates with evidence of cognitive impairment (based on reading ability and comprehension, will be excluded.
- •Female candidates who are pregnant (urine pregnancy test), lactating, or not using adequate birth control methods (self-report) will be excluded.
- •Candidates with injection phobia, or seeking treatment for opioid dependence will be excluded.
研究组 & 干预措施
Extended-Release Morphine + placebo stressor
Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. The placebo stressor will be administered on one day.
干预措施: Extended release morphine (Drug)
Extended-Release Morphine + placebo stressor
Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. The placebo stressor will be administered on one day.
干预措施: Placebo stressor (Drug)
Buprenorphine/Naloxone low dose + placebo stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day.
干预措施: Buprenorphine/Naloxone low dose (Drug)
Buprenorphine/Naloxone low dose + placebo stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day.
干预措施: Placebo stressor (Drug)
Buprenorphine/Naloxone moderate dose + placebo stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. The placebo stressor will be administered on one day.
干预措施: Buprenorphine/Naloxone moderate dose (Drug)
Buprenorphine/Naloxone moderate dose + placebo stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. The placebo stressor will be administered on one day.
干预措施: Placebo stressor (Drug)
Buprenorphine/Naloxone high dose + placebo stressor
Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. The placebo stressor will be administered on one day.
干预措施: Buprenorphine/Naloxone high dose (Drug)
Buprenorphine/Naloxone high dose + placebo stressor
Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. The placebo stressor will be administered on one day.
干预措施: Placebo stressor (Drug)
Extended-Release Morphine + active stressor
Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Extended release morphine (Drug)
Extended-Release Morphine + active stressor
Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Active stressor (Drug)
Buprenorphine/Naloxone low dose + active stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Buprenorphine/Naloxone low dose (Drug)
Buprenorphine/Naloxone low dose + active stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Active stressor (Drug)
Buprenorphine/Naloxone moderate dose + active stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Buprenorphine/Naloxone moderate dose (Drug)
Buprenorphine/Naloxone moderate dose + active stressor
Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Active stressor (Drug)
Buprenorphine/Naloxone high dose + active stressor
Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Buprenorphine/Naloxone high dose (Drug)
Buprenorphine/Naloxone high dose + active stressor
Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
干预措施: Active stressor (Drug)
结局指标
主要结局
Opioid price-inelasticity (economic demand)
时间窗: measured once (end of session) in each of the 8 experimental sessions over 7 weeks
demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task
次要结局
- Opioid Symptom Questionnaire: Agonist symptoms(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Opioid Symptom Questionnaire: Withdrawal symptoms(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Visual Analog Scale (VAS) ratings(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Profile of Mood States (POMS)(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Saliva cortisol level(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.)
- Blood pressure(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Heart rate(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Pupil diameter(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.)
- Plasma IL-1Ra level (µg/ml)(Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions)
- Plasma noradrenaline level(Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions)
- Plasma BDNF level (µg/ml)(Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions)
- Saliva alpha-amylase level(Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.)
研究者
Mark Greenwald, PhD
Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division
Wayne State University