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CompletedNCT03015246BOSUpdated Nov 10, 2020

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

A Phase 1/2 interventional study of Extended release morphine and Buprenorphine/Naloxone low dose in Heroin Dependence and Opioid Use Disorder, sponsored by Wayne State University. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2020-11-10.

Sponsored by Wayne State University · Phase 1/2, Interventional, and Basic science

Phase
Phase 1/2
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Heroin Dependence
  • Opioid Use Disorder
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
26 participants (actual)

Study arms

  • Placebo comparator
    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.

    Drug: Extended release morphine · Drug: Placebo stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone low dose · Drug: Placebo stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone moderate dose · Drug: Placebo stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone high dose · Drug: Placebo stressor

  • Experimental
    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.

    Drug: Extended release morphine · Drug: Active stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone low dose · Drug: Active stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone moderate dose · Drug: Active stressor

  • Experimental
    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.

    Drug: Buprenorphine/Naloxone high dose · Drug: Active stressor

Interventions

  • DrugExtended release morphine

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

  • DrugBuprenorphine/Naloxone low dose

    Buprenorphine/Naloxone dose of 1.4/0.36 mg/day

    Also known as: Zubsolv™ sublingual tablet

  • DrugBuprenorphine/Naloxone moderate dose

    Buprenorphine/Naloxone dose of 4.2/1.08 mg/day

    Also known as: Zubsolv™ sublingual tablet

  • DrugBuprenorphine/Naloxone high dose

    Buprenorphine/Naloxone dose of 12.8/3.16 mg/day

    Also known as: Zubsolv™ sublingual tablet

  • DrugActive stressor

    Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

  • DrugPlacebo stressor

    Lactose

05

What researchers measure

Primary outcomes

  1. Opioid price-inelasticity (economic demand)

    demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task

    Time frame: measured once (end of session) in each of the 8 experimental sessions over 7 weeks

Secondary outcomes

  1. 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)

    Time frame: 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.

  2. 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)

    Time frame: 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.

  3. 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).

    Time frame: 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.

  4. Profile of Mood States (POMS)

    72-item POMS questionnaire, which has several subscale scores

    Time frame: 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.

  5. Blood pressure

    Systolic/diastolic blood pressure (mm Hg)

    Time frame: 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.

  6. Heart rate

    Heart rate (beats/min)

    Time frame: 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.

  7. Pupil diameter

    Pupil diameter (mm) measured with digital pupillometer

    Time frame: 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.

  8. Plasma noradrenaline level

    Plasma noradrenaline level (µg/ml)

    Time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions

  9. Plasma BDNF level (µg/ml)

    Plasma brain derived neurotrophic factor level (pg/ml)

    Time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions

  10. Plasma IL-1Ra level (µg/ml)

    Plasma interleukin 1Ra level (pg/ml)

    Time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions

  11. Saliva cortisol level

    Saliva cortisol level (µg/dL)

    Time frame: 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.

  12. Saliva alpha-amylase level

    Saliva alpha-amylase level (U/dL)

    Time frame: 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.

06

Study locations

1 site
  • Vince and Associates
    Overland Park, Kansas 66212, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03015246
Lead sponsor
Wayne State University
Responsible party
Mark Greenwald, PhD (Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division, Wayne State University) — Principal investigator
First posted
Jan 10, 2017
Start date
Dec 2016
Primary completion
Jun 2020
Completion
Aug 2020
Last update
Nov 10, 2020

Study contacts

Mark Greenwald, PhD
principal investigator · Wayne State University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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