Pain Management Strategies for Chronic Pain

(TREETOP Trial)

Recruiting at 14 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

268 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find better ways to manage chronic pain for individuals already taking buprenorphine, a medication for pain and opioid addiction. It tests two new approaches: one involves working with a pain coach and peer to learn self-management skills (Pain Self-Management, PSM), and the other adjusts buprenorphine doses based on pain levels (Patient-Oriented Dosing, POD). Participants will join one of four groups, each receiving different combinations of these treatments. This trial suits those with opioid use disorder who are on a stable buprenorphine dose and face significant daily pain challenges. As a Phase 4 trial, the research focuses on understanding how these FDA-approved treatments can benefit more patients.

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.

What is the safety track record for these treatments?

Research has shown that the Pain Self-Management (PSM) program is generally easy for people to handle. Studies suggest that self-management techniques can reduce the need for opioids and help manage pain, making PSM a safe option for many with chronic pain.

For Patient-Oriented Dosing (POD), research indicates that adjusting the medication buprenorphine based on pain levels is well-tolerated. Studies have found that taking buprenorphine in divided doses, as POD involves, effectively manages pain without increasing side effects. Buprenorphine is safe in doses up to 32 mg per day, making it a reliable choice for managing chronic pain.

Overall, previous research has shown both PSM and POD to be safe. Prospective trial participants can expect these methods to be generally safe, with strong evidence supporting their use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for chronic pain management because they offer innovative approaches that go beyond standard care. Pain Self-Management (PSM) empowers patients with behavioral strategies to manage their pain, integrating personalized support through group and individual sessions. Patient-Oriented Dosing (POD) is another game-changer, allowing buprenorphine dosing to be adjusted based on individual pain levels, potentially offering more precise and effective relief. These methods aim to enhance patient autonomy and tailor pain management to each individual's needs, which could result in better outcomes compared to traditional fixed dosing regimens.

What evidence suggests that this trial's treatments could be effective for chronic pain?

This trial will evaluate different strategies for managing chronic pain. Participants in one arm will receive Pain Self-Management (PSM) alongside standard buprenorphine dosing. Studies have shown that PSM programs can help people with chronic pain feel better and improve their daily activities. These programs often involve working with a coach to learn how to handle pain daily, which can lead to using fewer opioids.

Another arm will test Patient-Oriented Dosing (POD) with PSM, where the medication buprenorphine is adjusted based on the participant's pain level. Research indicates that this personalized approach can effectively manage pain while continuing treatment for opioid use disorder. Both strategies in this trial aim to help people manage their pain better and rely less on opioids. ^{1 3 5 6 7}

Who Is on the Research Team?

Erin L Winstanley, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Erin Winstanley

Lead Sponsor

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK458655/

Pain Management and the Opioid Epidemic - NCBI Bookshelf A study of 1,477 adults prescribed opioids for chronic pain, for example, showed that patients who used lower or intermittent doses of opioids had pain outcomes ...

2. journals.lww.com journals.lww.com/pain/fulltext/2023/04000/opioid_dose_and_pain_effects_of_an_online_pain.24.aspx

Opioid dose and pain effects of an online pain self ... This low-burden online intervention could assist adults on LOT in reducing daily opioid use while self-managing pain symptom burdens.

3. bmj.com bmj.com/content/377/bmj-2021-066375

Efficacy of interventions to reduce long term opioid ... The pooled data on the effect of pain self-management programmes on pain and function accorded with previous evidence that pain self-management ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2805141

Reducing Opioid Use for Chronic Pain With a Group-Based ... This randomized clinical trial compares the efficacy of a multicomponent, group-based, self-management intervention vs usual care in reducing opioid use.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06855732

Pain Self-Management and Treatment Engagement for ... The goal of this study is to learn if Pain Self-Management (PSM) can improve chronic pain care in individuals with opioid misuse or opioid use disorder ...

6. research.va.gov research.va.gov/topics/pain.cfm

Pain Management Several studies have shown that using opioids for chronic pain may actually worsen pain and functioning.

7. cdc.gov cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

CDC Clinical Practice Guideline for Prescribing Opioids ... Opioid therapy is associated with small improvements in short-term (duration of 1 to <6 months) pain and function compared with placebo, with ...