Clinical Outcome Assessment Development for Opioid Use Disorder

Overseen By Cecilia L Bergeria, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must not be taking: Naltrexone

Disqualifiers: Pregnancy, Psychosis, Suicidal behavior, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to collect information about opioid craving so that the investigators can develop an opioid craving assessment to improve treatments for individuals with opioid use disorder. To collect this information, the investigators are recruiting individuals in treatment for opioid use disorder who will complete cue-induced opioid craving tasks where these individuals will: (1) look at pictures of neutral objects and touch neutral objects (e.g., water bottles or flashlights), (2) look at opioid-related images, and (3) look and touch opioid-related objects. Participants will then complete a one-on-one interview about the thoughts, feelings and physical sensations the participants experienced during the cue-induced craving session. Participants will also complete questionnaires and existing opioid craving assessments. Finally, participants will provide formal feedback about existing opioid craving assessments with cognitive interviews.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does exclude individuals receiving Naltrexone, so you may need to discuss your current medications with the trial team.

What data supports the effectiveness of this drug for opioid use disorder?

Research shows that buprenorphine, a key component of the treatment, is effective in reducing opioid cravings and use. It has been found to decrease the choice of high-dose cocaine in studies, suggesting its potential to reduce cravings and drug-seeking behavior in opioid use disorder. ^{1 2 3 4 5}

Is buprenorphine safe for treating opioid use disorder?

Buprenorphine has been shown to be safe for treating opioid dependence, with studies indicating no serious safety concerns. Some patients may experience mild side effects like injection site reactions or opioid-induced constipation, but overall, it is considered a safe option for managing opioid use disorder. ^{1 4 6 7 8}

How does the drug buprenorphine differ from other treatments for opioid use disorder?

Buprenorphine is unique because it acts as a mixed opioid agonist-antagonist, which means it can both activate and block opioid receptors, helping to reduce cravings and the salience of drug-associated cues. This dual action makes it effective in reducing opioid misuse and cravings, and it can also improve mental health symptoms in patients with opioid use disorder. ^{1 5 9 10 11}

Research Team

Cecilia L Bergeria, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 who are currently in treatment for opioid use disorder and have tested positive for opioids, excluding those on Naltrexone. It's not open to individuals with other substance disorders (except nicotine), pregnant or breastfeeding women, those at risk of incarceration, intoxicated persons, or people with recent suicidal behavior or serious psychiatric issues.

Inclusion Criteria

Opioid-positive urine sample at admission visit (excluding individuals receiving Naltrexone)

Current opioid use disorder per Diagnostic Statistical Manual (DSM)-5

I am 18 years old or older.

Exclusion Criteria

Have circumstances that would interfere with study participation (e.g., impending jail)

Being pregnant or breastfeeding, or may become pregnant during the trial

Positive for illicit substances except opioids and cannabis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cue-Induced Craving Tasks

Participants complete cue-induced opioid craving tasks involving exposure to neutral and opioid-related cues, followed by interviews and questionnaires.

3 sessions (approximately 1 hour each)

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the cue-induced craving tasks

4 weeks

Treatment Details

Interventions

• Neutral Cue-induced Craving
• Visual and Tactile Opioid Cue-induced Craving
• Visual Opioid Cue-induced Craving

Trial Overview The study aims to develop an assessment tool for measuring opioid craving by having participants engage with neutral items and opioid-related images and objects. They will then discuss their experiences in interviews and complete questionnaires about their cravings.

Participant Groups

Group I: No Craving Experimental Treatment 3 Interventions

Each participant will attend three sessions where the participant will experience three distinct cue-induced craving tasks in a randomized fashion.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Buprenorphine and buprenorphine/naloxone (BUP/NAL) significantly reduce opioid craving compared to placebo, indicating their efficacy as medications for opioid use disorder (OUD).

However, lower doses of buprenorphine are associated with higher craving levels, and in some studies, buprenorphine was linked to greater craving than methadone and extended-release naltrexone, suggesting that other MOUD may be more effective in managing cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on opioid craving in comparison to other medications for opioid use disorder: A systematic review of randomized controlled trials. Baxley, C., Borsari, B., Reavis, JV., et al.[2023]

In a study with seven male volunteers, buprenorphine pretreatment significantly reduced the choice of high doses of cocaine while increasing the preference for non-drug alternatives (tokens), suggesting its potential to help reduce cocaine use.

Despite the reduction in cocaine choice, participants still experienced significant intoxication effects from the combination of buprenorphine and cocaine, indicating that while buprenorphine may help curb cocaine use, the overall effects and interactions of these substances are complex and not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on the self-administration of cocaine by humans. Foltin, RW., Fischman, MW.[2019]

In a study involving 14 heroin-dependent volunteers maintained on buprenorphine, hydromorphone (HYD) showed minimal reinforcing effects in those who were abstinent from heroin, while non-abstainers experienced significant dose-related increases in HYD's reinforcing value.

The study found that while buprenorphine did not reduce the reinforcing effects of hydromorphone in non-abstainers, it did help reduce heroin craving in a dose-dependent manner, indicating that buprenorphine can effectively manage cravings even in the presence of other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance. Greenwald, MK., Johanson, CE., Schuster, CR.[2019]

Buprenorphine, administered in doses ranging from 1.5 to 8.0 mg/day, effectively reduced heroin craving and use in 85 heroin addicts over a maintenance period of 4 to 12 weeks, with 40 participants having no prior treatment.

In a discontinuation trial, those who underwent dose reductions experienced significantly more withdrawal symptoms and cravings compared to those who maintained a stable dose, indicating that careful management of dosage is crucial for successful treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine: an alternative to methadone for heroin dependence treatment. Resnick, RB., Galanter, M., Pycha, C., et al.[2013]

Chronic buprenorphine treatment effectively reduces cocaine intake in rats, but does not affect heroin consumption, indicating a selective efficacy for cocaine addiction.

Buprenorphine treatment enhances dopamine levels in the nucleus accumbens while attenuating the dopamine response to heroin, suggesting it may help reduce the appeal of drug-associated cues and drug-seeking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. Sorge, RE., Stewart, J.[2018]

Probuphine, an implantable formulation of buprenorphine, was evaluated in 12 heroin-dependent volunteers and showed a continuous and effective delivery of medication over 6 months, maintaining low withdrawal symptoms and cravings.

The study found that 59% of urine tests were opioid-negative during treatment, indicating effective management of opioid dependence, with only mild injection site reactions reported and no serious safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. White, J., Bell, J., Saunders, JB., et al.[2013]

A study involving 53 opioid-dependent patients showed that switching from buprenorphine to buprenorphine/naloxone was well-tolerated, with no significant issues reported during the transition.

Patients expressed a preference for buprenorphine/naloxone over buprenorphine, with 54% favoring the combination formulation due to its taste and ease of use, indicating it may be a more acceptable option for maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. Daulouède, JP., Caer, Y., Galland, P., et al.[2015]

In a study of 43 opioid-dependent patients switched from buprenorphine monotherapy to buprenorphine/naloxone for 24 weeks, the combination therapy effectively controlled cravings and withdrawal symptoms, with 91% of patients rating their management as satisfactory by the end of the study.

The addition of naloxone to buprenorphine significantly reduced the potential for misuse, as only 2% of patients attempted intravenous misuse, and none reported gratifying effects, indicating a safer profile for outpatient treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre. Montesano, F., Zaccone, D., Battaglia, E., et al.[2018]

Chronic treatment with buprenorphine (3.0 mg/kg/day) in rats significantly reduced their responses to sucrose-associated cues and decreased reinstatement of sucrose seeking, suggesting its potential to blunt drug-seeking behavior.

While buprenorphine did not significantly affect the dopamine response to sucrose or lab chow, it did increase basal dopamine levels, indicating a complex interaction with the brain's reward system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats. Hood, S., Sorge, RE., Stewart, J.[2014]

Chronic buprenorphine treatment does not affect the locomotor response to heroin but significantly enhances the response to cocaine, indicating a potential risk for increased cocaine use among opioid users on buprenorphine.

Buprenorphine effectively reduces drug-seeking behavior for both heroin and cocaine in rats, suggesting it may help manage cravings in opioid addiction, although it does not prevent stress-induced drug seeking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement. Sorge, RE., Rajabi, H., Stewart, J.[2019]

In a study of 43 patients with chronic non-cancer pain and opioid use disorder, switching to buprenorphine/naloxone (BuNa) significantly reduced opioid misuse, craving, and psychiatric symptoms such as depression and anxiety over a two-month follow-up.

Patients also reported a decrease in pain levels after the BuNa rotation, suggesting that this treatment could be an effective strategy for managing both pain and opioid dependence, although further research with larger sample sizes is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Opioid Rotation to Buprenorphine/Naloxone on Opioid Misuse, Craving, Mental Health, and Pain Control in Chronic Non-Cancer Pain Patients with Opioid Use Disorder. Schellekens, AFA., Veldman, SE., Suranto, ESD., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on opioid craving in comparison to other medications for opioid use disorder: A systematic review of randomized controlled trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine on the self-administration of cocaine by humans. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Buprenorphine: an alternative to methadone for heroin dependence treatment. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. [2015]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Opioid Rotation to Buprenorphine/Naloxone on Opioid Misuse, Craving, Mental Health, and Pain Control in Chronic Non-Cancer Pain Patients with Opioid Use Disorder. [2021]