Injectable Buprenorphine vs Naltrexone for Opioid Use Disorder

Overseen By Urooj Iqbal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Opioid agonists, antagonists

Must not be taking: Antidepressants, antipsychotics

Disqualifiers: Psychotic disorders, Polysubstance use, 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: 3

Duration: 3 months

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This project aims to elucidate the brain effects of opioid use disorder (OUD) treatments. The study will investigate the cognitive effects of extended-release preparations of a partial opioid agonist and an antagonist. To this end, the study will use up to three monthly injections of buprenorphine (XRBUP, Brixadi®) and naltrexone (XRNTX, Vivitrol®). Domain-specific brain activity will be induced by cognitive tasks and recorded with Magnetic Resonance Imaging. Participants will be imaged at baseline and in the interval between the 1st and 2nd injection and followed for up to three months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have a psychiatric disorder that requires medication, you may not be eligible to participate.

Is injectable buprenorphine and naltrexone safe for humans?

Research shows that both buprenorphine (used in forms like Subutex and Suboxone) and naltrexone (used as Vivitrol) have been studied for safety in treating opioid use disorder. Buprenorphine is effective but can be misused, while the combination with naloxone helps reduce this risk. Naltrexone is also used safely, but more research is needed to fully understand its safety in diverse patient groups. ^{1 2 3 4 5}

How is the drug Buprenorphine different from Naltrexone for opioid use disorder?

Buprenorphine is a partial agonist (activator) of opioid receptors, which helps reduce withdrawal symptoms and cravings, and is available in prolonged-release injectable forms that can improve patient comfort by reducing the need for daily dosing. Naltrexone, on the other hand, is an opioid antagonist (blocker) that prevents the effects of opioids and is also available as an extended-release injection, but it requires complete detoxification before starting treatment. ^{1 6 7 8 9}

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

Research shows that sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments for opioid use disorder, with each having different ways of working. Additionally, sublingual buprenorphine is noted as an effective maintenance treatment for opioid dependence. ^{1 2 7 9 10}

Who Is on the Research Team?

James Loughead, Ph.D.

Principal Investigator

University of Pennsylvania, Psychiatry

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with opioid use disorder, confirmed by medical assessment and tests. Participants must speak English, have a stable address and phone access. It's not for those with psychotic disorders, active liver disease, conditions affecting treatment safety or MRI contraindications. Women of childbearing age must use effective contraception.

Inclusion Criteria

I am prescribed opioids as my main pain medication.

I am open to trying long-lasting injectable treatments.

Diagnosed with OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records, and self-report

Exclusion Criteria

I have a psychiatric condition but only take medication for mild to moderate depression, anxiety, or ADHD without stimulants.

I am of childbearing age and do not use birth control.

My main substance use is not opioids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three once-a-month injections of either buprenorphine or naltrexone and complete weekly monitoring visits

3 months

3 visits (in-person) for injections, weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Naltrexone

Trial Overview The study compares monthly injections of two drugs: Buprenorphine (Brixadi®) and Naltrexone (Vivitrol®), to understand their effects on the brain in people with opioid addiction. Brain activity will be monitored through MRIs before and after treatments over three months.

How Is the Trial Designed?

Group I: Buprenorphine Experimental Treatment 1 Intervention

Study participants receive three once-a-month injections of buprenorphine and complete weekly monitoring visits.

Group II: Naltrexone Active Control 1 Intervention

Study participants receive three once-a-month injections of naltrexone and complete weekly monitoring visits.

Buprenorphine is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a study involving 570 adults with opioid use disorder, buprenorphine-naloxone was found to be more cost-effective than extended-release naltrexone, being preferred in 97% of cases at 24 weeks and 85% at 36 weeks based on quality-adjusted life-years (QALYs).

The analysis suggests that buprenorphine-naloxone is the better first-line treatment option, especially for patients needing detoxification before starting extended-release naltrexone, although the study had limitations such as a relatively short follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. Murphy, SM., McCollister, KE., Leff, JA., et al.[2020]

In a study involving 12 intravenous heroin users, buprenorphine/naloxone was self-administered significantly less often than buprenorphine or heroin, indicating a lower potential for misuse.

Participants reported lower 'drug liking' and 'desire to take the drug again' for buprenorphine/naloxone compared to buprenorphine alone, suggesting that this combination may be a safer option for treating opioid dependence while reducing the risk of misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Comer, SD., Sullivan, MA., Vosburg, SK., et al.[2022]

A survey of intravenous drug users in Helsinki revealed that 73% used buprenorphine as their primary drug, primarily for self-treating addiction or withdrawal symptoms.

The combination of buprenorphine and naloxone (Suboxone) was tried by 68% of respondents, but 80% reported negative experiences, suggesting that while it may help reduce buprenorphine abuse, its acceptance among users is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Alho, H., Sinclair, D., Vuori, E., et al.[2015]

In a study of 533 participants over 18 months after stopping extended-release buprenorphine injection (BUP-XR), 47% reported sustained opioid abstinence, with higher rates of abstinence linked to longer treatment durations.

More than 60% of participants showed stable or improved outcomes in health-related quality of life and mental health scores, indicating that BUP-XR has a long-term positive impact on recovery from opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. Boyett, B., Nadipelli, VR., Solem, CT., et al.[2023]

In a 24-week study involving 570 patients with opioid use disorder, those who were homeless had a significantly lower relapse rate when treated with extended-release naltrexone (51.6%) compared to buprenorphine-naloxone (70.4%).

Conversely, non-homeless patients had a higher relapse rate with extended-release naltrexone (70.9%) compared to buprenorphine-naloxone (53.1%), indicating that demographic factors like homelessness can influence the effectiveness of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. Nunes, EV., Scodes, JM., Pavlicova, M., et al.[2021]

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 involving 302 participants with cocaine dependence and a history of opioid dependence, buprenorphine + naloxone (BUP) combined with extended-release injectable naltrexone (XR-NTX) showed a significant reduction in cocaine use for those receiving 16 mg/day of BUP compared to placebo, indicating its potential effectiveness in this population.

However, no significant differences were observed in the primary outcome for the 4 mg/day BUP group compared to placebo, suggesting that higher doses may be necessary for efficacy, while adherence, retention, and adverse events were similar across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Ling, W., Hillhouse, MP., Saxon, AJ., et al.[2018]

In a study of 79 US military veterans with opioid use disorder, both extended-release injectable naltrexone (XR-NTX) and buprenorphine/naloxone (BUP-NX) showed similar treatment retention and outcomes over a 90-day period, indicating that both medications are effective options.

While the BUP-NX group had a higher prevalence of pain diagnoses, there were no significant differences in substance use outcomes, suggesting that both treatments can be safely used in veterans with various medical and psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Naloxone and Extended Release Injectable Naltrexone for the Treatment of Opioid Use Disorder Among a Veteran Patient Sample: A Retrospective Chart Review. Shirk, SD., Ameral, V., Kraus, SW., et al.[2021]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2022]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2021]

Citations

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

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. [2020]

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

Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. [2022]

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

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. [2015]

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

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. [2023]

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

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. [2021]

6. 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]

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

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018]

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

Buprenorphine Naloxone and Extended Release Injectable Naltrexone for the Treatment of Opioid Use Disorder Among a Veteran Patient Sample: A Retrospective Chart Review. [2021]

9. France pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. [2021]