Pain Management Strategies for Chronic Pain

(TREETOP Trial)

Recruiting at 12 trial locations

Overseen By Melessa Salay, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Jessica Merlin

Must be taking: Buprenorphine

Must not be taking: Naltrexone

Disqualifiers: Cancer-related pain, Pregnancy, 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: 17

Duration: 12 weeks

460 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require you to be on a stable dose of buprenorphine. If you are taking naltrexone, you cannot participate in the study.

Is buprenorphine safe for managing chronic pain?

Buprenorphine, used in various forms like Suboxone and Belbuca, is generally considered safe for managing moderate to severe pain and opioid dependence. However, it can cause complications during surgery and has potential drug interactions, so careful planning is needed when used with other medications. ^{1 2 3 4 5}

How is the drug used in the Pain Management Strategies for Chronic Pain trial different from other treatments?

The drug used in this trial, buprenorphine, is unique because it can be administered in various forms such as buccal (inside the cheek), sublingual (under the tongue), and transdermal (through the skin) patches, offering flexibility in pain management. It is also notable for its dual role in treating both chronic pain and opioid use disorder, making it a versatile option for patients with complex needs. ^{1 2 6 7 8}

What is the purpose of this trial?

This study seeks to improve the treatment of chronic pain in people who are taking buprenorphine (also known as Suboxone, Subutex, Zubsolv). The research study is testing two different interventions along with usual clinical care: 1. Pain Self-Management (PSM): an educational program in which individuals with chronic pain work with a trained pain coach and a pain peer to explore strategies to effectively manage the daily problems that arise from chronic pain. 2. Patient-Oriented Dosing (POD): an alternative dosing of buprenorphine which will be adjusted based on pain levels. The interventions will take place over a period of 12 weeks (3 months). Additionally, participants will complete surveys every 3 months for a period of 1 year (total of 5 survey visits). Participants will receive $50 compensation for each survey visit completed (up to $250 over one year) and can receive up to an additional $100 bonus compensation. There are risks associated with participating in the study, including breach of confidentiality, psychological distress caused by discussing difficult topics, and risks associated with the POD intervention.

Research Team

Jessica Merlin, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals with chronic pain who are also taking buprenorphine for opioid use disorder. Participants should be interested in learning to manage their pain or trying a new way of dosing their medication. Specific eligibility criteria were not provided, so it's important to contact the study team for more details.

Inclusion Criteria

Ability to speak, read, and understand English

Access to phone and/or internet

Documented diagnosis of Opioid Use Disorder (OUD) within <180 days (6 months) of a new treatment episode, ideally within 90 days (3 months)

Exclusion Criteria

I am currently taking 32mg of buprenorphine.

I am currently using injectable buprenorphine.

Are currently in jail, prison, or overnight facility as required by court of law or have pending legal action that could prevent participation in study activities

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Pain Self-Management (PSM) and Patient-Oriented Dosing (POD) interventions over 12 weeks

12 weeks

12 intervention sessions (6 group, 6 individual)

Follow-up

Participants complete surveys every 3 months for a period of 1 year to monitor outcomes

12 months

5 survey visits

Treatment Details

Interventions

• Pain Self-Management (PSM)
• Patient-Oriented Dosing (POD)

Trial Overview The study tests two interventions: Pain Self-Management (PSM), where participants learn from a coach and peer about managing chronic pain, and Patient-Oriented Dosing (POD), which adjusts buprenorphine dosage based on individual pain levels, alongside usual care over 12 weeks.

Participant Groups

Group I: Usual Care + Patient-Oriented Dosing (POD) Experimental Treatment 2 Interventions

Usual care, or "treatment as usual," refers to the standard of care that participants receive at their office-based addiction treatment (OBAT) clinic. This includes discussing issues related to chronic pain and opioid use (e.g., buprenorphine) with their provider and receiving clinical care for these conditions. Patient-oriented dosing (POD) is a promising approach to using buprenorphine or buprenorphine/naloxone for treating participants with both opioid use disorder (OUD) and chronic pain. POD allows titration of buprenorphine or buprenorphine/naloxone dosing up to 32mg/day, split into four doses per day, based on the participant's pain level.

Group II: Pain Self-Management (PSM) + Standard Buprenorphine Dosing Experimental Treatment 2 Interventions

Pain self-management (PSM) is a manualized behavioral intervention tailored for patients in outpatient-based addiction treatment (OBAT) programs. PSM consists of 12 intervention sessions, comprising 6 group sessions and 6 individual sessions. Participants will continue standard buprenorphine or buprenorphine/naloxone dosing as part of normal clinical care.

Group III: Pain Self-Management (PSM) + Patient-Oriented Dosing (POD) Experimental Treatment 2 Interventions

Pain self-management (PSM) is a manualized behavioral intervention tailored for patients in outpatient-based addiction treatment (OBAT) programs. PSM consists of 12 intervention sessions, comprising 6 group sessions and 6 individual sessions. Patient-oriented dosing (POD) is a promising approach to using buprenorphine or buprenorphine/naloxone for treating participants with both opioid use disorder (OUD) and chronic pain. POD allows titration of buprenorphine or buprenorphine/naloxone dosing up to 32mg/day, split into four doses per day, based on the participant's pain level.

Group IV: Usual Care + Standard Buprenorphine Dosing Active Control 2 Interventions

Usual care, or "treatment as usual," refers to the standard of care that participants receive at their office-based addiction treatment (OBAT) clinic. This includes discussing issues related to chronic pain and opioid use (e.g., buprenorphine) with their provider and receiving clinical care for these conditions. Participants will continue standard buprenorphine or buprenorphine/naloxone dosing as part of normal clinical care.

Pain Self-Management (PSM) is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Opioid use disorder
• Acute pain
• Chronic pain

Approved in European Union as Buprenorphine for:

• Opioid dependence
• Severe pain

Who Is Running the Clinical Trial?

Jessica Merlin

Lead Sponsor

Trials

1

Recruited

460+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

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]

Buprenorphine HCl buccal film (BBUP) significantly reduced pain in opioid-naive patients with chronic low back pain, showing a greater reduction in pain scores compared to placebo after 12 weeks of treatment.

BBUP was well tolerated, with common side effects including nausea and constipation, and a higher percentage of patients experienced at least a 30% reduction in pain compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain. Rauck, RL., Potts, J., Xiang, Q., et al.[2022]

Suboxone, which contains buprenorphine and naloxone, effectively blocks the effects of other opioids due to buprenorphine's strong binding to μ-opioid receptors, making it a useful treatment for opioid dependence.

Patients on Suboxone or Subutex may face challenges during procedures due to inadequate sedation and analgesia, highlighting the need for careful planning and understanding of buprenorphine's pharmacology to avoid complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine therapy: an increasing challenge in oral and maxillofacial surgery. Wasson, M., Beirne, OR.[2013]

Buprenorphine is a versatile medication designed for both pain relief and treatment of opioid use disorder, acting as a partial agonist at mu receptors and an antagonist at delta receptors, which helps manage pain while reducing the risk of misuse.

Various formulations of buprenorphine, including injectable, transdermal, and sublingual options, have been developed to cater to different patient needs, with specific combinations like Suboxone® including naloxone to deter misuse in opioid dependence treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and its formulations: a comprehensive review. Poliwoda, S., Noor, N., Jenkins, JS., et al.[2022]

Buprenorphine plus naloxone (Suboxone) is marketed as having a lower risk of abuse compared to buprenorphine alone (Subutex), but evidence supporting this claim is lacking, as noted in a review of the literature.

Transitioning from buprenorphine alone to the combination of buprenorphine/naloxone has not shown a decrease in risky behaviors, such as injection drug use among individuals with opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". Newman, RG., Gevertz, SG.[2021]

This case report highlights that effective pain management is achievable for patients with opioid use disorder (OUD) on extended-release buprenorphine (ER-buprenorphine) through individualized, multidisciplinary approaches, as demonstrated in three different clinical scenarios.

Strategies for managing acute pain in these patients can include supplemental sublingual buprenorphine, non-opioid medications, and short-term use of full opioid agonists, while addressing barriers such as provider bias and access to specialized care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain Management in Patients With Opioid Use Disorder on Extended-release Buprenorphine: A Case Report. South, AM., Oller, D., Lofwall, M., et al.[2023]

A systematic review of 25 randomized controlled trials found that transdermal buprenorphine is an effective treatment for chronic pain, with 10 out of 15 studies showing significant pain reduction compared to other pain medications or placebo.

Buccal buprenorphine also showed promise in managing chronic pain, with 2 out of 3 studies indicating clinically significant benefits, and importantly, no serious adverse effects were reported across all studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies. Aiyer, R., Gulati, A., Gungor, S., et al.[2019]

Buprenorphine is FDA-approved for treating opioid use disorder (OUD) and chronic pain, and it is generally better tolerated by patients compared to other opioids, with a favorable half-life and reduced risk of respiratory depression.

Despite its benefits, many healthcare providers lack training in prescribing buprenorphine, which could limit its use as a safer alternative for managing chronic pain and OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine for Chronic Pain Management: a Narrative Review. Vu, PD., Bansal, V., Chitneni, A., et al.[2023]

References

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

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

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

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain. [2022]

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

Buprenorphine therapy: an increasing challenge in oral and maxillofacial surgery. [2013]

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

Buprenorphine and its formulations: a comprehensive review. [2022]

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

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pain Management in Patients With Opioid Use Disorder on Extended-release Buprenorphine: A Case Report. [2023]

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

Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies. [2019]

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

Buprenorphine for Chronic Pain Management: a Narrative Review. [2023]