Buprenorphine for Opioid Use Disorder

Overseen By Joji Suzuki, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, CYP34A inducers

Disqualifiers: Substance use disorder, Chronic pain, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a human laboratory-based, randomized, cross-over study in which buprenorphine will be administered to healthy volunteers (n=22) in 3 separate inpatient 2-night visits, at least 1 week apart. At each visit, the participant will receive a single dose buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Participants will be given naltrexone to produce opioid blockade to eliminate the risk for opioid dependence in individuals without OUD. Timed blood samples will be collected up to 24 hours.

Do I need to stop taking my current medications for the trial?

The trial requires that you do not take certain medications, specifically those that are strong or moderate CYP34A inducers or inhibitors, in the past 30 days. If you are on such medications, you may need to stop them before participating.

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

Research shows that Buprenorphine, often combined with Naloxone (as in Suboxone), is effective in treating opioid use disorder by improving treatment outcomes. However, challenges like low adherence and misuse exist, which can be addressed with sustained release formulations. ^{1 2 3 4 5}

Is buprenorphine safe for humans?

Buprenorphine is generally considered safe for treating opioid dependence, with a lower risk of overdose compared to other opioids. However, it can still be abused, especially if not taken as prescribed, and there are risks if it is injected instead of taken as directed. ^{1 6 7 8 9}

What makes the drug Buprenorphine unique for treating opioid use disorder?

Buprenorphine is unique because it combines a partial mu-receptor agonist (buprenorphine) with an antagonist (naloxone) in a 4:1 ratio, which helps reduce the risk of misuse. It is administered sublingually (under the tongue), making it different from other treatments that may require different routes of administration. ^{10 11 12 13 14}

Eligibility Criteria

This trial is for English-speaking adults over 18 with a history of opioid use, either prescribed or not, in the past year. They must have stable vital signs and be in good health as confirmed by medical exams, lab tests, and EKG. It's not suitable for those outside these criteria.

Inclusion Criteria

I am 18 or older and speak English.

Your heart rate, blood pressure, and breathing rate should be within certain normal ranges before starting the trial.

You have used opioids before, whether for medical reasons or not.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive buprenorphine in 3 separate inpatient 2-night visits, with doses of 0.15mg IV, 8mg PO, or 16mg PO, at least 1 week apart.

6 weeks

3 visits (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Buprenorphine (Opioid Agonist)

Trial Overview The study is testing low-dose buprenorphine induction strategies on healthy volunteers to manage opioid dependence. Participants will receive different doses of buprenorphine across three sessions with naltrexone to prevent dependency.

Participant Groups

Group I: 8mg PO buprenorphine Experimental Treatment 1 Intervention

After the open-label period, the participant will receive 8mg PO, then 16mg PO will be administered in the following visit.

Group II: 16mg PO buprenorphine Experimental Treatment 1 Intervention

After the open-label period, the participant will receive 16mg PO, then 8mg PO will be administered in the following visit.

Group III: 0.15mg IV Dose Experimental Treatment 1 Intervention

The first dose administered will be fixed to an open-label 0.15mg IV dose.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Findings from Research

Buprenorphine is an opioid medication used for treating opioid dependence and managing moderate to severe pain, and it can be prescribed to pregnant women as part of their treatment for opioid addiction.

The chapter details a method for quantifying buprenorphine and its metabolite norbuprenorphine in meconium using liquid chromatography tandem mass spectrometry (LC-MS/MS), which is important for monitoring drug exposure in newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. Marin, SJ., McMillin, GA.[2016]

A study of 200 rural residents revealed that motivations for using nonprescribed buprenorphine shifted from initially seeking to avoid withdrawal and get high to maintaining abstinence from other drugs, indicating a complex relationship with self-treatment.

Participants with a history of treatment for opioid use disorder were more likely to use nonprescribed buprenorphine for self-treatment, suggesting that dissatisfaction with existing treatment options may drive individuals to seek alternatives outside of prescribed care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Motivations for Nonprescribed Buprenorphine Use Among Rural Appalachian Substance Users. McDonald, MJ., DeVeaugh-Geiss, AM., Chilcoat, HD., et al.[2023]

The novel weekly subcutaneous buprenorphine depot formulation, CAM2038, was found to effectively block the euphoric effects of opioids and suppress withdrawal symptoms in individuals with moderate-to-severe opioid use disorder, based on a study involving 47 participants.

Both doses of CAM2038 (24 mg and 32 mg) were well-tolerated and demonstrated significant efficacy in preventing opioid effects, making it a promising alternative to daily oral formulations that carry risks of misuse and nonadherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. Walsh, SL., Comer, SD., Lofwall, MR., et al.[2020]

In a study of 32 veterans over three years, those receiving buprenorphine/naloxone in a group setting had a significantly higher retention rate in treatment after one year (69%) compared to those treated individually (27%).

The study also found that 94% of urine samples from participants were negative for opioids, indicating effective management of opioid use disorder with buprenorphine/naloxone in a group format.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group medication management for buprenorphine/naloxone in opioid-dependent veterans. Berger, R., Pulido, C., Lacro, J., et al.[2014]

The study will involve 280 adults with opioid use disorder and aims to improve adherence to buprenorphine-naloxone treatment through two psychological interventions: contingency management (CM) and brief motivational interviewing plus substance-free activities and mindfulness (BSM).

The primary goal is to assess which intervention is more effective in promoting medication adherence, measured by attendance at physician appointments and the presence of buprenorphine in urine toxicology, with follow-up occurring 8 months after randomization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. Peter, SC., Murphy, JG., Witkiewitz, K., et al.[2023]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

Buprenorphine, approved for treating opiate dependence, has been found to have an abuse potential similar to that of traditional opioids like morphine, despite initial beliefs of its low abuse risk.

A study of 120 buprenorphine abusers revealed that the majority were middle-aged males with a significant history of early illicit drug use, highlighting a concerning trend of prescription medication abuse that requires increased awareness and vigilance among healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. Winslow, M., Ng, WL., Mythily, S., et al.[2020]

Buprenorphine (Subutex) is recognized for its improved safety profile in treating opioid dependence, particularly by reducing the risk of overdose compared to other opioids.

Despite its safety advantages, there are still risks associated with the diversion of buprenorphine for misuse, as evidenced by cases of attempted intravenous injection, highlighting the need for strict dispensing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. Feeney, GF., Fairweather, P.[2013]

Buprenorphine and its combination with naloxone (Suboxone) have been officially added to the list of approved medications for treating opioid dependence in federally certified treatment programs, alongside methadone and ORLAAM.

These medications will be subject to the same federal treatment standards as existing opioid treatments, ensuring consistent safety and efficacy protocols in managing opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid drugs in maintenance and detoxification treatment of opiate addiction; addition of buprenorphine and buprenorphine combination to list of approved opioid treatment medications. Interim final rule. [2013]

Suboxone (buprenorphine/naloxone) is a well-tolerated and effective treatment for opiate addiction, with significant positive psychological and behavioral changes observed in patients during the first month of therapy.

The initial phase of treatment is critical, as nearly 22.5% of patients dropped out within the first month, highlighting the need for thorough patient education about potential withdrawal symptoms to improve retention rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early experience with Suboxone maintenance therapy in Hungary. Demetrovics, Z., Farkas, J., Csorba, J., et al.[2015]

A study analyzing 5,970 emergency department visits in Italy found that benzodiazepines (BZD) and Z-drugs (ZD) are associated with a higher rate of adverse events (AEs) leading to hospitalization compared to opioids, particularly among younger patients and those with a history of substance abuse.

23% of BZD/ZD-related AEs were linked to drug abuse, and these cases often required hospitalization (52%), highlighting the significant health risks associated with the inappropriate use of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hospitalisations related to benzodiazepine, Z-drug, and opioid treatment in Italy: a claim on the risks associated with inappropriate use. Mattioli, I., Bettiol, A., Crescioli, G., et al.[2022]

Chronic use of intravenous bisphosphonates, like Zometa, can lead to bisphosphonate-related osteonecrosis of the jaws (BRONJ), which is a serious and painful condition that can have severe consequences for patients.

This case highlights the importance for dentists to recognize the early signs of BRONJ and consider treatment options, including conservative measures and potential jaw resection, to manage this complication effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-related osteonecrosis of the jaws--a case report. Kamoh, AK., Ogle, O.[2018]

Zoledronic acid (ZOL), administered as a single intravenous infusion once a year, effectively reduces the risk of vertebral and hip fractures in postmenopausal women with osteoporosis, and also lowers the incidence of future fractures in men and women with recent hip fractures.

ZOL is generally safe and well tolerated, with mild and transient flu-like symptoms occurring after the first infusion, making it a convenient option for patients who may struggle with compliance to oral bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid for prevention and treatment of osteoporosis. Recknor, C.[2018]

Intravenous zoledronic acid (Zol) is effective in reducing fracture risk in patients with postmenopausal osteoporosis and recent low-trauma hip fractures, showing improvements in bone mineral density and early reduction of bone remodeling markers.

Zol is generally well tolerated and offers a convenient once-a-year treatment option, making it suitable for older patients with adherence issues to oral medications, although it is not recommended for those with severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of zoledronic acid in the prevention and treatment of osteoporosis. Räkel, A., Boucher, A., Ste-Marie, LG.[2023]

References

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

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. [2016]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Assessing Motivations for Nonprescribed Buprenorphine Use Among Rural Appalachian Substance Users. [2023]

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

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Group medication management for buprenorphine/naloxone in opioid-dependent veterans. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. [2023]

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

Buprenorphine maintenance: a new treatment for opioid dependence. [2019]

7. Singapore pubmed.ncbi.nlm.nih.gov

Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. [2020]

8. Australia pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. [2013]

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

Opioid drugs in maintenance and detoxification treatment of opiate addiction; addition of buprenorphine and buprenorphine combination to list of approved opioid treatment medications. Interim final rule. [2013]

10. Hungary pubmed.ncbi.nlm.nih.gov

Early experience with Suboxone maintenance therapy in Hungary. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

Hospitalisations related to benzodiazepine, Z-drug, and opioid treatment in Italy: a claim on the risks associated with inappropriate use. [2022]

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

Bisphosphonate-related osteonecrosis of the jaws--a case report. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Zoledronic acid for prevention and treatment of osteoporosis. [2018]

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

Role of zoledronic acid in the prevention and treatment of osteoporosis. [2023]