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

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ClinicalTrials.gov Identifier: NCT03015246
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Mark Greenwald, PhD, Wayne State University

Tracking Information
First Submitted Date  ICMJE December 16, 2016
First Posted Date  ICMJE January 10, 2017
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE December 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
Opioid price-inelasticity (economic demand) [ Time Frame: measured once (end of session) in each of the 8 experimental sessions over 7 weeks ]
demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task
Original Primary Outcome Measures  ICMJE
 (submitted: January 5, 2017)
Opioid Use Urine Drug Testing [ Time Frame: Change is being assessed. Urine Drug Testing will occur during inpatient stay and be re-evaluated at 1, 2 and 3 month follow-up visits after completing the dose taper. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
  • Opioid Symptom Questionnaire: 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. ]
    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)
  • Opioid Symptom Questionnaire: 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. ]
    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)
  • Visual Analog Scale (VAS) ratings [ 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. ]
    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).
  • Profile of Mood States (POMS) [ 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. ]
    72-item POMS questionnaire, which has several subscale scores
  • Blood pressure [ 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. ]
    Systolic/diastolic blood pressure (mm Hg)
  • Heart rate [ 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. ]
    Heart rate (beats/min)
  • Pupil diameter [ 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. ]
    Pupil diameter (mm) measured with digital pupillometer
  • Plasma noradrenaline level [ Time Frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions ]
    Plasma noradrenaline level (µg/ml)
  • Plasma BDNF level (µg/ml) [ Time Frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions ]
    Plasma brain derived neurotrophic factor level (pg/ml)
  • Plasma IL-1Ra level (µg/ml) [ Time Frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions ]
    Plasma interleukin 1Ra level (pg/ml)
  • Saliva cortisol level [ 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. ]
    Saliva cortisol level (µg/dL)
  • Saliva alpha-amylase level [ 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. ]
    Saliva alpha-amylase level (U/dL)
Original Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2017)
  • Opioid Symptom Questionnaire (Self-Report Measure) [ Time Frame: Change is being assessed. Self-report measure will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
    Opioid Agonist (16 items) and Withdrawal (16 items) symptoms will be assessed using a 32-item inventory.
  • Visual Analog Scales (VAS) (Self-Report Measure) [ Time Frame: Change is being assessed. Self-report measure will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
    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).
  • Profile of Mood States (Self-Report Measure) [ Time Frame: Change is being assessed. Self-report measure will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
    Mood state will be measured using a modified Profile of Mood States with 72 adjectives.
  • Systolic blood pressure (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
  • Diastolic blood pressure (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
  • Heart rate (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
  • Respiration Rate (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
  • Oxygen saturation (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
  • Pupil diameter (physiological effects) [ Time Frame: Change is being assessed. Measurements will be obtained at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
Official Title  ICMJE Biobehavioral Studies of Opioid Seeking: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Heroin Dependence
  • Opioid Use Disorder
Intervention  ICMJE
  • Drug: Buprenorphine-Naloxone
    To blind the varying maintenance doses, on each protocol day the participant will always take a total of 4 tablets at the same time, with a mixture of active and placebo tablets. Total daily doses will differ, depending on the periods/weeks within each study phase.
    Other Name: Zubsolv™
  • Drug: Extended-release Morphine
    During each participant's first experimental week, morphine doses (tailored to each individual) will be administered orally prior to each of the first 2 inpatient experimental sessions.
    Other Name: Morphine
  • Drug: Yohimbine
    Yohimbine (or matching placebo)will be administered at 12:00pm on each of the experimental sessions.
    Other Name: Yohimbine hydrochloride powder
  • Drug: Hydrocortisone
    Hydrocortisone or matching placebo will be administered 45 min after Yohimbine.
    Other Name: Cortef™
  • Drug: Matching Placebo for Yohimbine
    Yohimbine (or matching placebo) will be administered at 12:00pm on each of the experimental sessions.
    Other Name: placebo yohimbine (lactose)
  • Drug: Matching Placebo for Hydrocortisone
    Hydrocortisone or matching placebo will be administered 45 min after Yohimbine.
    Other Name: placebo hydrocortisone (lactose)
Study Arms  ICMJE
  • Experimental: Buprenorphine-Naloxone

    Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablets.

    Every participant will be maintained two weeks at each dosage level, in randomized order, on Buprenorphine-Naloxone (Zubsolv™) doses of 1.4/0.36 mg/day, 4.2/1.08 mg/day, and 12.8/3.16 mg/day.

    Interventions:
    • Drug: Buprenorphine-Naloxone
    • Drug: Extended-release Morphine
    • Drug: Yohimbine
    • Drug: Hydrocortisone
    • Drug: Matching Placebo for Yohimbine
    • Drug: Matching Placebo for Hydrocortisone
  • Buprenorphine-Naloxone Stabilization
    After completing the three Buprenorphine-Naloxone maintenance-dose conditions, each participant will be stabilized on a daily dose of Buprenorphine-Naloxone 4.2/1.08 mg for one week, then the daily dose will be tapered over 3 weeks to 2.8/0.72 mg (week 1), 1.4/0.36 mg (week 2) and 0/0 mg (week 3).
    Intervention: Drug: Buprenorphine-Naloxone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 5, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Debra Kelsh, M.D. (913) 696-1601 ext 6160 DKelsh@altasciences.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03015246
Other Study ID Numbers  ICMJE BOS-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mark Greenwald, PhD, Wayne State University
Study Sponsor  ICMJE Wayne State University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Greenwald, PhD Wayne State University
PRS Account Wayne State University
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP