Opioid Medications for Opioid Use Disorder

Overseen By JOSHUA LILE, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Joshua A. Lile, Ph.D.

Must not be taking: Alcohol, Benzodiazepines, Barbiturates

Disqualifiers: Respiratory disease, Cardiovascular issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 days

31 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this protocol is to use probabilistic reinforcement learning choice tasks and magnetic resonance neuroimaging to demonstrate the impact of problematic opioid use and opioid withdrawal on dynamic decision-making and reveal the neurobehavioral and neurobiological processes underlying abnormal task performance. A second objective is to identify an appropriate dose of intravenous remifentanil for subsequent studies in physically dependent individuals with opioid use disorder.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a substance use disorder for substances other than opioids or nicotine that requires detoxification, you may not be eligible to participate.

Is oxycodone safe for human use?

Oxycodone, like other opioids, has been associated with risks of misuse, abuse, dependence, and withdrawal. Safety data from studies indicate that abuse-deterrent formulations like Xtampza ER are designed to reduce the potential for misuse, but the risk of dependence and adverse reactions remains, especially when used with other drugs. ^{1 2 3 4 5}

How does this drug differ from other drugs for opioid use disorder?

This drug may involve the use of opioid medications like methadone, buprenorphine, or naltrexone, which are effective in treating opioid use disorder by managing withdrawal, reducing cravings, and blocking the effects of opioids. What makes these treatments unique is the availability of new formulations, such as monthly depot injections, which can improve adherence and reduce misuse compared to traditional daily dosing. ^{6 7 8 9 10}

Research Team

JOSHUA LILE, Ph.D.

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for adults with moderate to severe opioid use disorder who have used opioids recently or are in withdrawal. They must speak English and, if female, use effective birth control. It excludes those with other substance disorders needing detox (except nicotine), MRI contraindications, respiratory risks, seeking SUD treatment, poor veins (for remifentanil session), significant diseases or psychiatric disorders affecting compliance.

Inclusion Criteria

I am using an effective form of birth control.

Able to speak and read English

Must meet moderate/severe criteria for moderate/severe opioid use disorder, report recent prescription or illicit opioid use, and be opioid dependent, as evidenced by either a urine sample positive for recent opioid use or being in frank withdrawal during screening.

Exclusion Criteria

At risk for respiratory complications and have predictors of difficult bag mask ventilation (e.g., dentures, very full beard), in case emergency respiratory intervention is needed.

I don't have any major health or mental issues that would stop me from following the study's requirements.

Contraindications for MRI scanning (e.g., pacemaker, metal implants, claustrophobia, or any other implanted medical device).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete a gambling task during oxycodone and placebo administration, with an optional remifentanil dose-ranging session for those with a history of IV opioid use

9 days

Inpatient enrollment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Oxycodone
• Remifentanil

Trial Overview The study tests how opioid dependency and withdrawal affect decision-making using tasks and brain imaging. It aims to understand the related neurobehavioral processes and find a suitable dose of intravenous remifentanil for future research on individuals dependent on opioids.

Participant Groups

Group I: Placebo treatment followed by active treatment Experimental Treatment 2 Interventions

Participants complete a gambling task during placebo administration and then complete the same gambling task during oxycodone administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Group II: Active treatment followed by placebo treatment Experimental Treatment 2 Interventions

Participants complete a gambling task during oxycodone administration and then complete the same gambling task during placebo administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Who Is Running the Clinical Trial?

Joshua A. Lile, Ph.D.

Lead Sponsor

Trials

6

Recruited

120+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A significant increase in reports of abuse, misuse, and dependence related to prescription opioids was observed from 2003 to 2018, with 16,506 reports in EudraVigilance and 130,293 in the FDA Adverse Events Reporting System.

Fentanyl and oxycodone were particularly associated with abuse concerns, while tramadol and oxycodone showed stronger links to drug dependence and withdrawal, highlighting the need for careful monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS). Chiappini, S., Vickers-Smith, R., Guirguis, A., et al.[2022]

Xtampza ER, an abuse-deterrent formulation of extended-release oxycodone, demonstrated significant pain relief in patients with chronic low back pain, showing a mean reduction in pain intensity of -1.56 compared to placebo over 12 weeks.

The study, involving 740 participants, found that Xtampza ER was well tolerated with an adverse event profile similar to other opioids, and it resulted in fewer patients needing rescue medication compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain. Katz, N., Kopecky, EA., O'Connor, M., et al.[2022]

The abuse-deterrent formulation OxyM-ER (oxycodone myristate extended-release) may not provide effective pain management for cancer patients with low-calorie or low-fat diets, as its efficacy can be influenced by dietary intake.

An interdisciplinary approach, including dietary modifications, can enhance pain control for patients switched to OxyM-ER, demonstrating the importance of considering individual patient circumstances in opioid management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Food on Bioavailability of Oxycodone Myristate: A Case Report. Nguyen, TP., Hagiwara, Y., Pies, C., et al.[2022]

Xtampza® ER (oxycodone DETERx®) is an extended-release opioid formulation designed to deter abuse, and studies show that even when physically manipulated (crushed or chewed), it maintains its extended-release pharmacokinetic profile, making it less likely to be abused compared to immediate-release formulations.

In contrast, when OxyContin is crushed, it loses its extended-release properties and behaves like immediate-release oxycodone, highlighting Xtampza ER's potential as a safer option for patients needing chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza&#174; ER (oxycodone DETERx&#174; formulation): A review of published studies. Gudin, J.[2020]

Oxycodone consumption has significantly increased over the past two decades, surpassing morphine in 2008, yet much of its pharmacokinetic data is outdated, primarily from the 1990s.

Recent studies have provided crucial information on oxycodone's effects in special populations (like neonates and the elderly) and highlighted important drug interactions, particularly with CYP450 enzymes, which can affect its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Kinnunen, M., Piirainen, P., Kokki, H., et al.[2020]

Physicians perceive methadone and buprenorphine as more effective than extended-release naltrexone for treating opioid use disorder, especially in patients with co-occurring mental health disorders, highlighting a need for better education on the efficacy of all treatment options.

Insurance obstacles, particularly prior authorization requirements, are the most significant barriers to prescribing buprenorphine and naltrexone, suggesting that policy changes are necessary to improve access to these effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mixed-method comparison of physician-reported beliefs about and barriers to treatment with medications for opioid use disorder. Haffajee, RL., Andraka-Christou, B., Attermann, J., et al.[2021]

Over 2 million Americans have opioid use disorder, which is partly due to overprescribing, highlighting the need for better opioid stewardship and management strategies by physicians.

Three FDA-approved medications—methadone, buprenorphine, and naltrexone—are effective for treating opioid use disorder, but successful outcomes are best achieved through comprehensive, interprofessional management plans rather than relying solely on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. Witt, L., Butler, F.[2019]

Methadone is the most effective medication for treating opioid use disorder (OUD), as it helps suppress withdrawal symptoms and has strong evidence supporting its efficacy, especially with longer treatment durations leading to better social outcomes.

New formulations of buprenorphine and naltrexone, along with take-home naloxone programs, aim to improve safety and adherence in OUD treatment, addressing issues like relapse and overdose risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication Treatment of Opioid Use Disorder. Bell, J., Strang, J.[2021]

Methadone and buprenorphine-naloxone are effective long-term maintenance medications for opioid use disorders (OUDs), positively impacting the health of individuals with opioid addiction.

Despite their effectiveness, the use of buprenorphine and naltrexone is limited due to stigma and barriers in access to treatment, highlighting the need for improved education and resources in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of opioid addiction treatment and related preclinical research. Kreek, MJ., Reed, B., Butelman, ER.[2023]

The review of 18 studies indicates that treating ADHD in patients with opioid use disorder (OUD) can lead to better retention in OUD treatment programs and improvements in ADHD severity.

While the specific medications for OUD treatment could not be prioritized, the findings suggest that addressing ADHD symptoms is important for reducing illicit substance abuse in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review. Ramey, OL., Bonny, AE., Silva Almodóvar, A., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS). [2022]

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

A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain. [2022]

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

The Impact of Food on Bioavailability of Oxycodone Myristate: A Case Report. [2022]

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

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza&#174; ER (oxycodone DETERx&#174; formulation): A review of published studies. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A mixed-method comparison of physician-reported beliefs about and barriers to treatment with medications for opioid use disorder. [2021]

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

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. [2019]

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

Medication Treatment of Opioid Use Disorder. [2021]

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

Current status of opioid addiction treatment and related preclinical research. [2023]

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

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review. [2023]