Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence

Opioid Use Disorder Clinical Trial

— BOS  

Official title:

Biobehavioral Studies of Opioid Seeking: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03015246
• Other study ID #: BOS-1
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2016
• Est. completion date: August 2020

Study information

• Verified date: November 2020
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heroin Dependence
• Opioid Use Disorder

Intervention

Drug:
• Extended release morphine
Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.
• Buprenorphine/Naloxone low dose
Buprenorphine/Naloxone dose of 1.4/0.36 mg/day
• Buprenorphine/Naloxone moderate dose
Buprenorphine/Naloxone dose of 4.2/1.08 mg/day
• Buprenorphine/Naloxone high dose
Buprenorphine/Naloxone dose of 12.8/3.16 mg/day
• Active stressor
Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet
• Placebo stressor
Lactose

Locations

Country	Name	City	State
United States	Vince and Associates	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Wayne State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Opioid price-inelasticity (economic demand)	demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task	measured once (end of session) in each of the 8 experimental sessions over 7 weeks
Secondary	Opioid Symptom Questionnaire: Agonist symptoms	Total opioid agonist symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher opioid 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.
Secondary	Opioid Symptom Questionnaire: Withdrawal symptoms	Total opioid withdrawal symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher 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.
Secondary	Visual Analog Scale (VAS) ratings	VAS ratings will measure "liking", "good drug effect," "bad drug effect," "stimulated," "sedated", "[preferred opioid] craving", and "cigarette craving". Each VAS is scored from 0 (not at all) to 100 (extremely).	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.
Secondary	Profile of Mood States (POMS)	72-item POMS questionnaire, which has several subscale scores	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.
Secondary	Blood pressure	Systolic/diastolic blood pressure (mm Hg)	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.
Secondary	Heart rate	Heart rate (beats/min)	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.
Secondary	Pupil diameter	Pupil diameter (mm) measured with digital pupillometer	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.
Secondary	Plasma noradrenaline level	Plasma noradrenaline level (µg/ml)	Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
Secondary	Plasma BDNF level (µg/ml)	Plasma brain derived neurotrophic factor level (pg/ml)	Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
Secondary	Plasma IL-1Ra level (µg/ml)	Plasma interleukin 1Ra level (pg/ml)	Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
Secondary	Saliva cortisol level	Saliva cortisol level (µg/dL)	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.
Secondary	Saliva alpha-amylase level	Saliva alpha-amylase level (U/dL)	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.