Buprenorphine for Opioid Use Disorder

(Optimal Bup Trial)

Overseen By Jackie Goldman

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Rhode Island Hospital

Must be taking: Buprenorphine

Disqualifiers: Pregnant, Allergy to buprenorphine, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a higher dose of buprenorphine (24 mg) is more effective than the standard dose (16 mg) for individuals with opioid use disorder, particularly those who have used fentanyl. Buprenorphine treats opioid use disorder. The trial aims to determine if the higher dose helps participants stay in treatment, reduces their use of non-prescribed opioids, curbs cravings, and lowers overdose risk. It includes two groups: one receiving the standard dose and the other receiving the higher dose. Individuals diagnosed with moderate to severe opioid use disorder and a history of fentanyl use are well-suited for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those whose medications might interact seriously with buprenorphine. It's best to discuss your current medications with the trial team to see if they might be a concern.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that higher doses of buprenorphine, such as 24 mg daily, can safely treat opioid use disorder. Studies have found no major safety issues with these doses. Patients on these doses required fewer emergency visits, indicating that the treatment is generally well-tolerated. The FDA has already approved buprenorphine for treating opioid use disorder, further supporting its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Buprenorphine for opioid use disorder is unique because it offers a higher maintenance dose option that could be more effective for individuals with a history of fentanyl use. Most standard treatments for opioid use disorder, like methadone or lower doses of buprenorphine, aim to stabilize patients but may not fully address cravings in those who have used potent opioids like fentanyl. Researchers are excited about the high-dose buprenorphine (24 mg) because it aligns with pharmacodynamic principles suggesting it could better control cravings and improve patient outcomes, all while maintaining safety and tolerability. This expanded dosing range provides a new avenue for personalized treatment strategies that might offer better support for those with more severe substance use histories.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

This trial will compare two different daily maintenance doses of buprenorphine for opioid use disorder. Research has shown that higher doses of buprenorphine can improve treatment outcomes for individuals with opioid use disorder. Specifically, those taking more than 24 mg daily had fewer emergency room or hospital visits. This suggests that higher doses might help patients remain in treatment longer and reduce the risk of opioid-related issues. While the usual dose is 16 mg, the FDA has approved 24 mg as the highest safe dose for individuals with a history of fentanyl use. Overall, higher doses of buprenorphine have shown promise in helping people stay in treatment and reducing harm from opioid use. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe opioid use disorder, specifically those who have used fentanyl. Participants must speak English and be starting or already receiving buprenorphine treatment. They should have a history of fentanyl use confirmed by tests or self-report.

Inclusion Criteria

I speak English.

My doctor says I have a serious opioid addiction.

I am starting or already on buprenorphine for opioid addiction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a 16 mg or 24 mg daily maintenance dose of buprenorphine

6 months

Monthly visits for urine drug screens and self-reports

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Data collection from statewide health systems

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine

Trial Overview The study compares two doses of buprenorphine: a high dose (24 mg) versus the standard dose (16 mg) in patients using fentanyl. It looks at how well each dose keeps patients in treatment, reduces non-prescribed opioid use, lessens cravings, and prevents overdoses.

How Is the Trial Designed?

Group I: High Maintenance Daily Dose (24mg) Experimental Treatment 1 Intervention

The experimental intervention is a high daily maintenance dose of buprenorphine (24 mg) plus any usual clinical care the participant receives at the clinic. This high daily dose is the upper limit of the FDA-approved dose range and was selected based on preclinical studies, clinician anecdotes, case reports, and retrospective analyses suggesting improved effectiveness of higher buprenorphine doses among patients with a history of fentanyl use. Underlying pharmacodynamic principles support that the 24 mg daily dose of buprenorphine is likely to be well-tolerated, safe, and better control cravings among people with a history of fentanyl use.

Group II: Standard Maintenance Daily Dose (16mg) Active Control 1 Intervention

The control intervention is the FDA-recommended target daily maintenance dose of buprenorphine (16 mg) plus any usual clinical care the participant receives at the clinic.

Who Is Running the Clinical Trial?

Rhode Island Hospital

Lead Sponsor

Trials

275

Recruited

71,400+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Published Research Related to This Trial

A unique strategy using intravenous microdosing of buprenorphine allowed for the treatment of opioid use disorder (OUD) in a patient experiencing acute pain without causing withdrawal symptoms or worsening pain.

This approach enabled the successful weaning off full agonist opioids after discharge, demonstrating a potential method for managing OUD while addressing acute pain effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of intravenous buprenorphine microdosing to initiate medication for opioid use disorder in a patient with co-occurring pain: case report. Bodnar, A., Diffenderffer, C., Jablonski, LA., 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]

Buprenorphine is a safe and effective treatment for opioid use disorder (OUD) in emergency departments, acting as a partial mu-opioid receptor agonist with a long half-life and a ceiling effect that reduces the risk of overdose and withdrawal symptoms.

Implementing a buprenorphine program in the ED requires a comprehensive approach that includes medication-assisted treatment, counseling, and addressing the stigma associated with opioid replacement therapies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. Cisewski, DH., Santos, C., Koyfman, A., et al.[2019]

Buprenorphine/naloxone has a unique pharmacology that provides a ceiling effect on its cardio-respiratory depressant properties, making it potentially safer than other opioids, especially at higher doses.

Data from various safety monitoring systems indicate that buprenorphine/naloxone has a favorable safety profile compared to other opioids and psychotropic drugs, suggesting it may reduce the risk of overdose-related morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs. Howland, RH.[2015]

A retrospective study of 199 buprenorphine exposure cases from 2009 to 2018 showed that the majority of incidents were related to suicide attempts and overdoses in individuals with substance abuse issues, but no deaths were reported, indicating a relatively safe profile for buprenorphine.

The study found that while neurological symptoms were common (83%), respiratory symptoms were rare (13%), and the severity of most cases was low, with 80% classified as mild, suggesting that buprenorphine has a lower risk of severe respiratory depression compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine exposures in adolescents and adults: a 10-year experience of a French Poison Control Center. Boulamery, A., von Fabeck, K., Glaizal, M., et al.[2021]

In a clinical trial with 428 participants, weekly and monthly subcutaneous (SC) buprenorphine depot formulations were found to be noninferior to daily sublingual (SL) buprenorphine with naloxone in treating opioid use disorder, showing similar response rates and urine test results for opioid use.

The SC buprenorphine group demonstrated a statistically superior cumulative distribution function (CDF) for no illicit opioid use compared to the SL buprenorphine group, suggesting that depot formulations may offer additional benefits in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. Lofwall, MR., Walsh, SL., Nunes, EV., et al.[2022]

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]

A 12-month study involving 384 opioid-dependent patients in Germany showed that buprenorphine-naloxone is highly effective and safe, with low rates of serious adverse events (1.2%) and no reported deaths.

The treatment led to significant improvements in mental health and quality of life, with a 57.1% retention rate, and 96.7% of patients who remained in treatment continued with buprenorphine-naloxone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care. Apelt, SM., Scherbaum, N., Gölz, J., et al.[2015]

Citations

1. nih.gov nih.gov/news-events/news-releases/higher-doses-buprenorphine-may-improve-treatment-outcomes-people-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ... Those taking daily doses of more than 24 mg of buprenorphine went 50% longer before having a subsequent emergency or inpatient health care visit ...

2. nida.nih.gov nida.nih.gov/news-events/news-releases/2024/09/higher-doses-of-buprenorphine-may-improve-treatment-outcomes-for-people-with-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ... Those taking daily doses of more than 24 mg of buprenorphine went 50% longer before having a subsequent emergency or inpatient health care visit ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.16600

Dose‐specific clinical outcomes in patients with opioid use ... These data indicate that higher dosing of buprenorphine can confer a physiological benefit which, in turn, may improve outcomes and reduce harm ...

4. library.samhsa.gov library.samhsa.gov/sites/default/files/high-dose-buprenorphine-report-pep24-02-013.pdf

Listening Session: Use of High Dose Buprenorphine for the ... ✓ Canadian data regarding improved outcomes at higher (>24 mg) sublingual doses are lacking, but comparisons by serum levels obtained with buprenorphine ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2824049

Association of Daily Doses of Buprenorphine With Urgent ... These results suggest that higher doses of buprenorphine are associated with lower acute care utilization and could provide benefits to patients.

6. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1401676/full

Reconsidering the usefulness of long-term high-dose ... Buprenorphine is a safe medication and has minimal side effects when taken at approved doses. The addiction field should continue to strive for ...