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

NCT ID: NCT03015246

Last Updated: 2020-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2020-08-31

Brief Summary

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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

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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.

Conditions

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Heroin Dependence Opioid Use Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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.

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Extended release morphine

Intervention Type DRUG

Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.

Placebo stressor

Intervention Type DRUG

Lactose

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone low dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 1.4/0.36 mg/day

Placebo stressor

Intervention Type DRUG

Lactose

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone moderate dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 4.2/1.08 mg/day

Placebo stressor

Intervention Type DRUG

Lactose

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone high dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 12.8/3.16 mg/day

Placebo stressor

Intervention Type DRUG

Lactose

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.

Group Type EXPERIMENTAL

Extended release morphine

Intervention Type DRUG

Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.

Active stressor

Intervention Type DRUG

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone low dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 1.4/0.36 mg/day

Active stressor

Intervention Type DRUG

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone moderate dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 4.2/1.08 mg/day

Active stressor

Intervention Type DRUG

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

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.

Group Type EXPERIMENTAL

Buprenorphine/Naloxone high dose

Intervention Type DRUG

Buprenorphine/Naloxone dose of 12.8/3.16 mg/day

Active stressor

Intervention Type DRUG

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

Interventions

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Extended release morphine

Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.

Intervention Type DRUG

Buprenorphine/Naloxone low dose

Buprenorphine/Naloxone dose of 1.4/0.36 mg/day

Intervention Type DRUG

Buprenorphine/Naloxone moderate dose

Buprenorphine/Naloxone dose of 4.2/1.08 mg/day

Intervention Type DRUG

Buprenorphine/Naloxone high dose

Buprenorphine/Naloxone dose of 12.8/3.16 mg/day

Intervention Type DRUG

Active stressor

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

Intervention Type DRUG

Placebo stressor

Lactose

Intervention Type DRUG

Other Intervention Names

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Zubsolv™ sublingual tablet Zubsolv™ sublingual tablet Zubsolv™ sublingual tablet

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wayne State University

OTHER

Sponsor Role lead

Responsible Party

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Mark Greenwald, PhD

Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mark Greenwald, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

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Vince and Associates

Overland Park, Kansas, United States

Site Status

Countries

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United States

Other Identifiers

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BOS-1

Identifier Type: -

Identifier Source: org_study_id