Pain Self-Management and Patient-Oriented Dosing for Pain and in Retention Opioid Treatment (TREETOP)

Pain Self-Management and Patient-Oriented Dosing for Pain and Retention in Office-based Addiction Treatment: a Randomized 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pain; Opioid Use Disorder
• Intervention / Treatment: Behavioral: Usual Care; Drug: Standard Buprenorphine Dosing Condition; Drug: Patient-Oriented Dosing (POD); Behavioral: Pain Self-Management (PSM)

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Melessa Salay, MPH; Phone Number: 412-586-9849; Email: TREETOP@pitt.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Outpatient Addiction Treatment Services (OATS)
      • Contact: Research Team; Email: HFitzsimons@som.umaryland.edu
      • Principal Investigator: Eric Weintraub, MD
    • Baltimore, Maryland, United States, 21223
      • Alcohol and Drug Abuse Program (ADAP) - UM Addiction Treatment Center
      • Contact: Research Team; Email: HFitzsimons@som.umaryland.edu
      • Principal Investigator: Eric Weintraub, MD
    • Baltimore, Maryland, United States, 21224
      • Comprehensive Care Practice (CCP) - Johns Hopkins Bayview Medical Center
      • Contact: Research Team; Email: TREETOP@pitt.edu
      • Principal Investigator: Sophia Purekal, MD
    • Hagerstown, Maryland, United States, 21740
      • Wells House
      • Contact: Research Team; Email: HFitzsimons@som.umaryland.edu
      • Principal Investigator: Eric Weintraub, MD
  • Oregon
    • Portland, Oregon, United States, 97209
      • Central City Concern (CCC)
      • Contact: Research Team; Email: treetop@ohsu.edu
      • Principal Investigator: Jonathan Robbins, MD
    • Portland, Oregon, United States, 97233
      • Recovery Works Northwest (RWNW)
      • Contact: Research Team; Email: treetop@ohsu.edu
      • Principal Investigator: Jonathan Robbins, MD
    • Portland, Oregon, United States, 97239
      • OHSU Harm Reduction Bridges to Care (HRBR)
      • Contact: Research Team; Email: treetop@ohsu.edu
      • Principal Investigator: Jonathan Robbins, MD
    • Portland, Oregon, United States, 97239
      • OHSU Internal Medicine Clinic (IMC)
      • Contact: Research Team; Email: treetop@ohsu.edu
      • Principal Investigator: Jonathan Robbins, MD
  • Pennsylvania
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Latterman Family Health Center
      • Contact: Research Team; Phone Number: 412-852-8499; Email: TREETOP@pitt.edu
      • Principal Investigator: Jessica Merlin, MD, PhD, MBA
    • New Kensington, Pennsylvania, United States, 15068
      • UPMC St. Margaret Family Health Center
      • Contact: Research Team; Phone Number: 412-852-8499; Email: TREETOP@pitt.edu
      • Principal Investigator: Jessica Merlin, MD, PhD, MBA
    • Pittsburgh, Pennsylvania, United States, 15219
      • UPMC Internal Medicine Recovery Engagement Program (IM-REP)
      • Contact: Research Team; Phone Number: 412-852-8499; Email: TREETOP@pitt.edu
      • Principal Investigator: Jessica Merlin, MD, PhD, MBA
  • West Virginia
    • Martinsburg, West Virginia, United States, 25401
      • WVU Crisis Support & Recovery Center
      • Contact: Research Team; Phone Number: 304-290-9159; Email: lychoo@hsc.wvu.edu
      • Principal Investigator: Dorothy Van Oppen, MD
    • Morgantown, West Virginia, United States, 26505
      • WVU Chestnut Ridge Comprehensive Addiction Treatment Program (COAT)
      • Contact: Research Team; Phone Number: 304-290-9159; Email: lychoo@hsc.wvu.edu
      • Principal Investigator: Dorothy Van Oppen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Adults at least 18 years old from participating clinics
2. Ability to speak, read, and understand English
3. Capable of providing informed consent
4. Access to phone and/or internet
5. Documented diagnosis of Opioid Use Disorder (OUD)

6. Within <180 days (6 months) of a new treatment episode, ideally within 90 days (3 months)

   • New treatment episode is defined as not having received prescribed buprenorphine treatment in an outpatient setting for OUD in the prior 30 days (1 month)
7. On a stable dose of an oral or sublingual buprenorphine mono or combination product (<4 times per day, daily dosage <32 mg) for at least 7 days during incident new episode of care
8. Have high impact chronic pain (Grade 3), based on the Graded Chronic Pain Scale-Revised (GCPS-R)

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Under 18 years of age
2. Have cancer-related pain
3. 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
4. Currently prescribed 32mg of an oral or sublingual buprenorphine mono or combination product
5. Currently prescribed an injectable formulation of buprenorphine
6. Pregnancy or intention to become pregnant within 4 months of enrollment
7. Currently prescribed naltrexone
8. History of hypersensitivity to buprenorphine that a clinician-determined caused serious rash/hives/pruritus, bronchospasm, angioneurotic edema, or anaphylactic shock

Individuals with common comorbidities, such as depression, anxiety, or alcohol, methamphetamine, and other substance use disorders will not be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care + Standard Buprenorphine Dosing; 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.	Behavioral: Usual Care; 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.; Drug: Standard Buprenorphine Dosing Condition; Participants will continue standard buprenorphine or buprenorphine/naloxone dosing as part of normal clinical care.
Experimental: Usual Care + Patient-Oriented Dosing (POD); 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.	Behavioral: Usual Care; 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.; Drug: Patient-Oriented Dosing (POD); Patient-oriented dosing (POD) is a promising approach to using buprenorphine or buprenorphine/naloxone to treat individuals with both OUD and chronic pain. It is based on existing evidence related to buprenorphine for the treatment of pain. POD allows participants to receive a daily dosage of bup up to 32mg/day, split up to 4 times per day. A response-guided dosing strategy, in which buprenorphine or buprenorphine/naloxone doses will be titrated based on a participant response, will be used to identify a dose regimen that is safe and effective. Due to inter-individual pharmacokinetic/pharmacodynamic variability, POD dosing will be individualized based on a participant's pain intensity and interference.
Experimental: Pain Self-Management (PSM) + Standard Buprenorphine Dosing; 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.	Drug: Standard Buprenorphine Dosing Condition; Participants will continue standard buprenorphine or buprenorphine/naloxone dosing as part of normal clinical care.; Behavioral: Pain Self-Management (PSM); Pain self-management (PSM) is a manualized behavioral intervention consisting of 12 sessions, comprising 6 group and 6 individual sessions. The first session will be individual, followed by a group session, and then alternating weekly for the remainder of the intervention. Individual sessions will be led by a staff Interventionist trained in the pain self-management intervention. The interventionist will guide participants through a PSM study manual, providing education, teaching associated skills, and assisting with goal setting. Group sessions will be led by a Peer Facilitator who has experience with chronic pain, opioid use disorder, and buprenorphine treatment. These sessions will not have specific content but will serve as supportive forums for participants to discuss their experiences with the intervention, share tips for managing chronic pain, and provide mutual support.
Experimental: Pain Self-Management (PSM) + Patient-Oriented Dosing (POD); 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.	Drug: Patient-Oriented Dosing (POD); Patient-oriented dosing (POD) is a promising approach to using buprenorphine or buprenorphine/naloxone to treat individuals with both OUD and chronic pain. It is based on existing evidence related to buprenorphine for the treatment of pain. POD allows participants to receive a daily dosage of bup up to 32mg/day, split up to 4 times per day. A response-guided dosing strategy, in which buprenorphine or buprenorphine/naloxone doses will be titrated based on a participant response, will be used to identify a dose regimen that is safe and effective. Due to inter-individual pharmacokinetic/pharmacodynamic variability, POD dosing will be individualized based on a participant's pain intensity and interference.; Behavioral: Pain Self-Management (PSM); Pain self-management (PSM) is a manualized behavioral intervention consisting of 12 sessions, comprising 6 group and 6 individual sessions. The first session will be individual, followed by a group session, and then alternating weekly for the remainder of the intervention. Individual sessions will be led by a staff Interventionist trained in the pain self-management intervention. The interventionist will guide participants through a PSM study manual, providing education, teaching associated skills, and assisting with goal setting. Group sessions will be led by a Peer Facilitator who has experience with chronic pain, opioid use disorder, and buprenorphine treatment. These sessions will not have specific content but will serve as supportive forums for participants to discuss their experiences with the intervention, share tips for managing chronic pain, and provide mutual support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Pain Interference as Assessed by the PROMIS SF v1.0 - Pain Interference 4a at 3 months Post-baseline	The PROMIS Pain Interference - Short Form 4a is a validated, self-report 4-item tool assessing pain interference over the past 7 days. The PROMIS SF v1.0 - Pain Interference 4a consists of 4 questions and uses a 5-point scale, ranging from 1 (not at all) to 5 (very much). The total raw score equals the sum the values of the response to each question. The raw score is converted to a T-score. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like pain interference, a T-score of 60 is one SD worse than average. That is, a person has more problems with pain hindering activities. By comparison, a pain interference T-score of 40 is one SD better than average. Change = 3 month score - baseline score	Baseline, 3 Months
Proportion of Participants Retained in buprenorphine Treatment at 3 months Post-baseline	Proportion retained is defined as # completed visits divided by # scheduled visits	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Overall Pain as Assessed by the PEG at 3 months Post-baseline	The Pain, Enjoyment, and General Activity (PEG) Scale is a validated, self-report 3-item tool assessing pain intensity and interference over the past week. The PEG scale consists of 3 separate numerical scales. Each scale has ratings ranging from 0-10. The PEG score is calculated by averaging the three numbers; a higher score indicates greater pain. Change = 3 month score - baseline score	Baseline, 3 Months
Change from Baseline in Pain Catastrophizing as Assessed by the Pain Catastrophizing Questionnaire-6-item at 3 months Post-baseline	The Pain Catastrophizing Scale is a validated, self-report 6-item tool assessing assess pain catastrophizing for chronic pain. The PCS-6 uses a 5-point scale, ranging from 0 (not at all) to 4 (all the time). The total score ranges from 0 to 24, with higher score representing greater catastrophic thinking. Change = 3 month score - baseline score	Baseline, 3 Months
Proportion of Participants Taking any MOUD at 3-, 6-, 9- and 12-months Post-baseline	Measured by self-report and medical chart extraction	3 Months, 6 Months, 9 Months, 12 Months
Change from Baseline in Self-efficacy as Assessed by the PROMIS Self-Efficacy for Managing Symptoms SF-4a at 3 months Post-baseline	The PROMIS Self-Efficacy for Managing Symptoms - Short Form 4a is a validated, self-report 4-item tool assessing current level of confidence to managing symptoms in relation to a chronic condition. The PROMIS SF v1.0 - Pain Interference 4a consists of 4 questions and uses a 5-point scale, ranging from 1 (I am not confident at all) to 5 ( I am very confident). The total raw score equals the sum the values of the response to each question. The raw score is converted to a T-score. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. A higher PROMIS T-score represents more of the concept being measured. For example, a T-score of 55 on the PROMIS Self-Efficacy for Managing Emotions indicates that the respondent has greater self-efficacy for managing their emotions than the general chronic condition population (i.e., half a standard deviation higher). Change = 3 month score - baseline score	Baseline, 3 Months
Number of Days Non-prescribed Opioids were Used in the past 30 days as Assessed by the Modified ASI at 3-months Post-baseline	The modified ASI is a validated, self-report tool which includes questions from the Addiction Severity Index section on drug and alcohol use and includes questions about specific opioids used. The number of days in the last 30 that a participant reports using heroin, fentanyl, and/or opioid analgesics (percocet, oxycodone, oxycontin, vicodin, dilaudid, hydrocodone, hydromorphone, morphine, or codeine) will be summed for the outcome "Number of days non-prescribed opioids were used in the past 30 days." Number of days may range from 0 to 90.	3 Months
Total score on the IMPOWR Opioid Misuse Screening scale at 3 months Post-baseline	The IMPOWR Opioid Misuse Screening scale is an exploratory, self-report scale consisting of 4 questions about the use of prescribed pain medications. Each question response ranges from Never (0) to Almost Always (4) with a possible summed score ranging from 0 to 16, with higher scores indicating more severe misuse.	3 Months

Collaborators and Investigators

• Sponsor: Jessica Merlin
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Jessica S Merlin, MD, PhD, MBA, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: buprenorphine; pain self-management
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Pain; Neurologic Manifestations; Narcotic-Related Disorders; Chronic Pain; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: STUDY23080191; RM1DA055311 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will comply with the HEAL Public Access and Data Sharing Policy (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/research/heal-public-access-data-sharing-policy) and data for this study will be available to the public through the IMPOWR Dissemination Education and Coordination Center (IDEA-CC) (https://heal.nih.gov/research/clinical-research/integrative-management-chronic-pain).
• IPD Sharing Time Frame: De-identified data will be made available within 18 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: Access to trial IPD may be made available to individuals that submit a request along with the required documents to the IMPOWR data committee. Data access requires approval by the IMPOWR data committee and the individual must agree to comply with the data sharing policies of IMPOWR and HEAL.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No