Pain Management Strategies for Chronic Pain

(TREETOP Trial)

Recruiting in Palo Alto (17 mi)

+12 other locations

Overseen by Jessica Merlin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Jessica Merlin

Must be taking: Buprenorphine

Must not be taking: Naltrexone

Disqualifiers: Cancer-related pain, Pregnancy, others

No Placebo Group

Prior Safety Data

Trial Summary

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.

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.

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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.

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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

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Central City Concern (CCC) Portland, OR

Recovery Works Northwest (RWNW) Portland, OR

Alcohol and Drug Abuse Program (ADAP) - UM Addiction Treatment Center Baltimore, MD

Outpatient Addiction Treatment Services (OATS) Baltimore, MD

More Trial Locations

Who Is Running the Clinical Trial?

Jessica Merlin Lead Sponsor

National Institute on Drug Abuse (NIDA) Collaborator

References

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

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. [2016] Buprenorphine (Suboxone, Zubsolv, Buprenex, Butrans, etc.) is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Pregnant women may be prescribed buprenorphine as part of a treatment plan for opioid addiction. This chapter quantitates buprenorphine and norbuprenorphine in meconium by liquid chromatography tandem mass spectrometry (LC-MS/MS).

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] Buprenorphine HCl buccal film has been developed for treating chronic pain utilizing BioErodible MucoAdhesive (BEMA(®)) delivery technology. Buccal buprenorphine (BBUP; Belbuca(TM), Endo Pharmaceuticals) was evaluated for the management of moderate to severe chronic low back pain (CLBP) requiring around-the-clock analgesia in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-naive patients.

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

Buprenorphine therapy: an increasing challenge in oral and maxillofacial surgery. [2013] Suboxone is a 4:1 mixture of buprenorphine and naloxone and Subutex is buprenorphine alone. The high affinity μ-receptor binding of buprenorphine (Suboxone and Subutex) renders other opioids ineffective. Inadequate procedural sedation, inadequate analgesia, and significant drug interactions complicate the treatment of patients taking Suboxone or Subutex. Careful planning and an understanding of buprenorphine pharmacology can minimize potential perioperative complications in patients taking Suboxone or Subutex.

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

Buprenorphine and its formulations: a comprehensive review. [2022] Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations.

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] In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5.

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

Pain Management in Patients With Opioid Use Disorder on Extended-release Buprenorphine: A Case Report. [2023] Persons with opioid use disorder (OUD) are receiving extended-release buprenorphine (ER-buprenorphine) for treatment of OUD. There are no clinical guidelines for management of patients with OUD on ER-buprenorphine experiencing acute or chronic pain. This case report describes 3 patient-involved, multidisciplinary approaches for pain management in various clinical scenarios, including a scheduled knee replacement, emergent surgery for an ischemic limb, and management of chronic pain from metastatic malignancy. These cases illustrate that adequate analgesia for patients who have received ER-buprenorphine is possible, and approaches can be individualized, with shared decision making between providers and patients addressing all barriers to optimize treatment outcomes. Options for acute pain management that can be considered include supplemental sublingual buprenorphine, nonopioid adjuncts, and short courses of full opioid agonists. Potential barriers that impact OUD and acute/chronic pain are provider bias, limited access to palliative care clinicians with addiction medicine training, and payor restrictions to adding sublingual buprenorphine for patients that are on ER-buprenorphine. Additional training for clinicians and other members of the health care team is recommended to improve patient-involved care of persons with OUD experiencing pain.

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

Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies. [2019] Clinical studies demonstrate that buprenorphine is a pharmacologic agent that can be used for the treatment of various types of painful conditions. This study investigated the efficacy of 5 different types of buprenorphine formulations in the chronic pain population. The literature was reviewed on PubMed/MEDLINE, EMBASE, Cochrane Database, clinicaltrials.gov, and PROSPERO that dated from inception until June 30, 2017. Using the population, intervention, comparator, and outcomes method, 25 randomized controlled trials were reviewed involving 5 buprenorphine formulations in patients with chronic pain: intravenous buprenorphine, sublingual buprenorphine, sublingual buprenorphine/naloxone, buccal buprenorphine, and transdermal buprenorphine, with comparators consisting of opioid analgesics or placebo. Of the 25 studies reviewed, a total of 14 studies demonstrated clinically significant benefit with buprenorphine in the management of chronic pain: 1 study out of 6 sublingual and intravenous buprenorphine, the only sublingual buprenorphine/naloxone study, 2 out of 3 studies of buccal buprenorphine, and 10 out of 15 studies for transdermal buprenorphine showed significant reduction in pain against a comparator. No serious adverse effects were reported in any of the studies. We conclude that a transdermal buprenorphine formulation is an effective analgesic in patients with chronic pain, while buccal buprenorphine is also a promising formulation based on the limited number of studies.

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

Buprenorphine for Chronic Pain Management: a Narrative Review. [2023] The aim of this review is to educate healthcare professionals regarding buprenorphine for the use of opioid use disorder (OUD) as well as for chronic pain management. This review provides physicians and practitioners with updated information regarding the distinct characteristics and intricacies of prescribing buprenorphine.