Buprenorphine for Opioid Use Disorder

(Optimal Bup Trial)

Overseen By Rachel Wightman, MD

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

Trial Summary

What is the purpose of this trial?

The investigators aim to test the effectiveness of a high maintenance daily dose of buprenorphine (24 mg) for improving outcomes among patients who used fentanyl compared to the standard daily dose (16 mg). The main question it aims to answer is: will patients who are randomly assigned to the high 24 mg maintenance dose, as compared to patients randomly assigned to the standard 16 mg maintenance dose, have improved retention in buprenorphine treatment (primary outcome), improved treatment response based on use of non-prescribed opioids (secondary outcome), decreased opioid cravings (secondary outcome), and decreased risk of fatal and non-fatal opioid overdose (exploratory outcome).

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.

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

Research shows that Buprenorphine is an effective treatment for opioid use disorder, helping people recover by reducing misuse and improving treatment outcomes. Sustained-release formulations of Buprenorphine can address issues like misuse and nonadherence, making it a reliable option for long-term treatment. ^{1 2 3 4 5}

Is buprenorphine safe for humans?

Buprenorphine is generally considered safe for humans, with studies showing it has fewer side effects and less risk of respiratory issues compared to other opioids. It is used to treat opioid dependence and has a high safety profile, even when combined with naloxone to prevent misuse. While some symptoms like neurological effects can occur, serious complications are rare, and it is associated with a lower risk of overdose deaths. ^{6 7 8 9 10}

How is the drug Buprenorphine unique for treating opioid use disorder?

Buprenorphine is unique because it can be administered as a weekly depot injection, which helps prevent misuse and ensures consistent medication levels, unlike daily oral forms that can be misused or skipped. Additionally, it can be initiated without stopping other opioid pain medications, making it easier for patients with co-occurring pain to start treatment. ^{1 2 4 11 12}

Eligibility Criteria

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 18 years old or older.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. 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]

2. 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]

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

Buprenorphine utilization among all Washington State residents' based upon prescription monitoring program data - Characteristics associated with two measures of retention and patterns of care over time. [2021]

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

Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. [2019]

5. United States 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. [2022]

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

Buprenorphine infrequently found in fatal overdose in New York City. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Buprenorphine exposures in adolescents and adults: a 10-year experience of a French Poison Control Center. [2021]

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

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

9. Germany 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. [2015]

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

The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice. [2018]

11. England 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. [2023]

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

Association of Project ECHO Training With Buprenorphine Prescribing by Primary Care Clinicians in Minnesota for Treating Opioid Use Disorder. [2023]