NCT03015246

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Dec 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2016

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

December 16, 2016

Completed
25 days until next milestone

First Posted

Study publicly available on registry

January 10, 2017

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2020

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2020

Completed
Last Updated

November 10, 2020

Status Verified

November 1, 2020

Enrollment Period

3.5 years

First QC Date

December 16, 2016

Last Update Submit

November 6, 2020

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (12)

  • 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.

  • 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.

  • +7 more secondary outcomes

Study Arms (8)

Extended-Release Morphine + placebo stressor

PLACEBO COMPARATOR

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 morphineDrug: Placebo stressor

Buprenorphine/Naloxone low dose + placebo stressor

EXPERIMENTAL

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 doseDrug: Placebo stressor

Buprenorphine/Naloxone moderate dose + placebo stressor

EXPERIMENTAL

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 doseDrug: Placebo stressor

Buprenorphine/Naloxone high dose + placebo stressor

EXPERIMENTAL

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 doseDrug: Placebo stressor

Extended-Release Morphine + active stressor

EXPERIMENTAL

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 morphineDrug: Active stressor

Buprenorphine/Naloxone low dose + active stressor

EXPERIMENTAL

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 doseDrug: Active stressor

Buprenorphine/Naloxone moderate dose + active stressor

EXPERIMENTAL

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 doseDrug: Active stressor

Buprenorphine/Naloxone high dose + active stressor

EXPERIMENTAL

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 doseDrug: Active stressor

Interventions

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

Extended-Release Morphine + active stressorExtended-Release Morphine + placebo stressor

Buprenorphine/Naloxone dose of 1.4/0.36 mg/day

Also known as: Zubsolv™ sublingual tablet
Buprenorphine/Naloxone low dose + active stressorBuprenorphine/Naloxone low dose + placebo stressor

Buprenorphine/Naloxone dose of 4.2/1.08 mg/day

Also known as: Zubsolv™ sublingual tablet
Buprenorphine/Naloxone moderate dose + active stressorBuprenorphine/Naloxone moderate dose + placebo stressor

Buprenorphine/Naloxone dose of 12.8/3.16 mg/day

Also known as: Zubsolv™ sublingual tablet
Buprenorphine/Naloxone high dose + active stressorBuprenorphine/Naloxone high dose + placebo stressor

Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet

Buprenorphine/Naloxone high dose + active stressorBuprenorphine/Naloxone low dose + active stressorBuprenorphine/Naloxone moderate dose + active stressorExtended-Release Morphine + active stressor

Lactose

Buprenorphine/Naloxone high dose + placebo stressorBuprenorphine/Naloxone low dose + placebo stressorBuprenorphine/Naloxone moderate dose + placebo stressorExtended-Release Morphine + placebo stressor

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vince and Associates

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Heroin DependenceOpioid-Related Disorders

Interventions

BuprenorphineNaloxone

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

MorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Study Officials

  • Mark Greenwald, PhD

    Wayne State University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: 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)
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division

Study Record Dates

First Submitted

December 16, 2016

First Posted

January 10, 2017

Study Start

December 1, 2016

Primary Completion

June 1, 2020

Study Completion

August 1, 2020

Last Updated

November 10, 2020

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will not share

Locations