Clinical trial NCT03015246: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
Official title: Biobehavioral Studies of Opioid Seeking: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heroin Dependence
Opioid Use Disorder
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2017-01-10
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 4x2 within-subject crossover design: 4 medication conditions (morphine first, then 3 doses of buprenorphine/naloxone), crossed with 2 stress conditions (placebo vs. stress \[yohimbine + hydrocortisone\], nested within medication conditions)
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

At the end of the study participants will be detoxified from the Buprenorphine/Naloxone medication over a 3-week outpatient period.

Study participants will be scheduled for one separate in-person visit at 1 month after week 11. At this follow-up visit participants will be asked to provide a urine sample and to complete questionnaires that ask about drug craving and use, withdrawal symptoms, risky situations for drug use, coping with stress, and consequences experienced from using drugs or being abstinent.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Opioid price-inelasticity (economic demand)
timeFrame: measured once (end of session) in each of the 8 experimental sessions over 7 weeks
Secondary outcomes:
measure: Opioid Symptom Questionnaire: Agonist symptoms
timeFrame: 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.
measure: Opioid Symptom Questionnaire: Withdrawal symptoms
timeFrame: 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.
measure: Visual Analog Scale (VAS) ratings
timeFrame: 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.
measure: Profile of Mood States (POMS)
timeFrame: 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.
measure: Blood pressure
timeFrame: 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.
measure: Heart rate
timeFrame: 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.
measure: Pupil diameter
timeFrame: 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.
measure: Plasma noradrenaline level
timeFrame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
measure: Plasma BDNF level (µg/ml)
timeFrame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
measure: Plasma IL-1Ra level (µg/ml)
timeFrame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
measure: Saliva cortisol level
timeFrame: 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.
measure: Saliva alpha-amylase level
timeFrame: 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.
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince and Associates
state: Kansas
Study officials:
affiliation: Wayne State University
name: Mark Greenwald, PhD
role: PRINCIPAL_INVESTIGATOR
References: