CClinicalTrials.gg
CompletedNCT03698669TOPPSUpdated Jan 8, 2026Results posted

Treating Chronic Pain in Buprenorphine Patients in Primary Care Settings

An interventional study of Treating Opioid Patients' Pain and Sadness (TOPPS) and Health Education (HE) in Opioid-Related Disorders, sponsored by Boston University. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-01-08.

Sponsored by Boston University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
163
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

Treating Opioid Patients' Pain and Sadness (TOPPS) focuses on the relationship of pain, depression, opioid and other substance misuse, and functioning. It has a structured agenda, uses behavioral activation, involves explicit and ongoing psychoeducation, and includes a behavioral health specialist (BHS) trained extensively in the nature of pain and opioid misuse, including how to assess for red flags of opioid relapse. Devised specifically for primary care patients receiving buprenorphine, TOPPS is collaborative (PCP, BHS, and patient) and focuses on pain and physical symptoms in order to decrease the need to turn to substance misuse to avoid pain, and to foster patient's abilities to achieve their long-term life goals. In this study, TOPPS is compared to a health education contact-control condition among 250 persons with opioid use disorder recruited from two primary care based buprenorphine programs. The investigators will provide both interventions over 3 months, and follow the patients for a total of 12 months in order to observe both short-term and longer-term effects of TOPPS.

Read the detailed description

Nearly 2.5 million individuals in the United States have opioid use disorder (OUD), with the vast majority (2 million) reporting abuse of prescription opioids. Patients with a history of substance use are particularly vulnerable to experiencing pain. Indeed, a large percentage of patients with OUD who receive the effective opioid agonist treatments (OAT) buprenorphine or methadone (MMT), report that pain preceded any use of addictive substances, and that the primary reason for starting opioid use was to reduce pain. Among methadone patients, 37-61% suffer from chronic pain that is often severe and interferes with daily activities. Similarly, in studies of chronic pain in buprenorphine patients, approximately 48% of patients report chronic pain. OAT recipients report far higher rates of chronic pain than the wider US population.

Chronic pain has been associated with negative substance use outcomes in persons receiving buprenorphine for opioid detoxification and in people receiving MMT. Providers may prioritize the treatment of substance use in OUD patients, leaving the concurrent pain untreated. Lack of treatment encourages patients to use illicit opioids for pain relief. Indeed, for persons using buprenorphine, greater pain severity in a given week was significantly associated with increased likelihood of opioid use in the following week.

Pain contributes to other negative outcomes. Pain is an independent risk factor for suicide including in samples of substance use disorder patients. Further, compared to MMT patients without pain, those with pain have significantly greater health problems and psychological distress. Pain, poor health, and low energy are the most commonly cited reasons that OAT patients are physically inactive. The continued physical and social problems in patients with pain influence the perception of (lack of) treatment benefits by both patients and providers.

Duration of opioid agonist treatment (OAT) is a key predictor of long-term abstinence and outcomes improve across a variety of domains if patients remain in care for at least one year. Although buprenorphine is a growing ambulatory treatment, retention in care remains problematic. Across practice sites and, despite variations in visit frequency, the 12-month retention rate ranges from 50-80% with the majority of treatment drop-out occurring during the first three months of treatment. Though few studies have yet examined the role of pain, pain has been found to negatively impact buprenorphine treatment retention.

Studies estimate that approximately one third to one half of MMT and buprenorphine recipients suffer from depression. Several studies have reported that opioid dependent patients with chronic pain have greater depressive symptoms and a greater probability of occupational disability compared to patients with lower level or no chronic pain. Amongst MMT patients, higher psychiatric distress is associated with lower general functioning. Methadone counselors report difficulty treating patients with chronic pain due in part to these patients' co-occurring psychiatric symptoms. In the only study of antidepressant treatment for depressed persons initiating buprenorphine, the investigators found in a secondary analysis that pain is prevalent, interferes with functioning, and its severity plateaus after one month of buprenorphine. Importantly, as with chronic pain, depressive symptoms have been associated with greater likelihood of relapse to opioid use in OAT patients. The substantial overlap of pain and depression in OAT patients suggest that functioning may improve most when depression and pain are simultaneously treated in an integrated fashion that is theoretically-based.

TOPPS is a type of cognitive behavioral therapy (CBT) that consists of three main components: 1) psychoeducation about pain, depression, opioid misuse, their interaction, and the maintaining role of avoidance; 2) coaching in being an informed, activated patient; and 3) behavioral activation with a focus on acceptance. Modern behavioral activation is idiographic and responsive to each patient's unique environment, needs, and goals. The function of a behavior is analyzed, and if the function is avoidance (e.g., of social contact, personal engagement, or physical activity), the behavior is targeted for change. Patients are taught to consider behavioral options, and to choose an option inconsistent with avoidance. There is an implicit attitude of acceptance of thoughts and feelings, as behavior is not dependent on changing thoughts and feelings. Behavior activation for depression focuses on helping patients to set goals in meaningful life areas, and then to break down long-term goals into smaller weekly goals. This process is incompatible with behavioral avoidance and instead, encourages patients to approach meaningful life goals. Barriers that arise in achieving short-term goals are addressed in treatment.

TOPPS focuses on the relationship of pain, depression, opioid and other substance misuse, and functioning. It has a structured agenda, uses behavioral activation, involves explicit and ongoing psychoeducation, and includes a BHS trained extensively in the nature of pain and opioid misuse and relapse. Devised specifically for primary care patients receiving buprenorphine, TOPPS is collaborative (physician, interventionist, and patient) and focuses on depression, pain and physical symptoms in order to decrease the need to turn to substance misuse to avoid pain, increase overall functioning and to foster patient's abilities to achieve their long-term life goals.

02

Conditions studied

  • Opioid-Related Disorders

Keywords

  • Depression
  • Pain
  • Cognitive behavioral therapy (CBT)
  • Buprenorphine
  • Behavioral health specialist (BHS)
  • Primary care provider (PCP)
03

In context

Opioid-Related Disorders

1,411 studies on the registry are indexed under Opioid-Related Disorders; 290 are open to participants now.

This study's enrollment of 163 is above the median of 63 across 1,123 interventional studies indexed under Opioid-Related Disorders.

Browse Opioid-Related Disorders studies →

Lead sponsor

Boston University is the lead sponsor of 266 studies on the registry; 37 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 24 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Between 18 and 65 years of age
  2. Have chronic pain, defined as pain duration for at least three months with a mean score of 4 or higher on the Brief Pain Inventory (BPI) Pain Interference Scale
  3. Pain severity of 4 or higher on a numerical rating scale (0-10) indicating "worst pain in the last week"
  4. If using an antidepressant, the dose must be stable for the previous 2 months
  5. Has received buprenorphine from the current primary care provider for at least the last month
  6. Continuing buprenorphine with no plan to taper dose for the next 12 months
  7. Score of ≥4 on Personal Health Questionnaire-9 instrument (at least "mild" depression severity)
  8. Gives informed consent to participate in the study.

Exclusion criteria

Exclusion Criteria:

  1. Expected surgery in the next 3 months
  2. Pain thought to be due to cancer, infection, or inflammatory arthritis
  3. Greater than or equal to 10 days of cocaine/crack/methamphetamine use in the past month
  4. Current (past month) mania or past year psychosis as determined via Structured Clinical Interview for DSM-5 (SCID) Module's A and B/C
  5. Lifetime diagnosis of schizophrenia or other chronic psychotic condition as determined by the study PI
  6. Planning to stop using buprenorphine in the next 6 months
  7. Pregnancy or planned pregnancy in the next 6 months.
  8. Greater than 8 homeless nights in the past month
  9. Suicide ideation or behavior requiring immediate attention
  10. Not able to provide informed consent
  11. Not able to complete interviews in English
  12. Unable to provide names and contact information for at least two verifiable locator persons who will know where to find them in the future.
  13. Greater than or equal to 45 days without a phone in the past 3 months/no reliable access to phone
  14. Headache/migraine as the only site of pain
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
163 participants (actual)

Study arms

  • Experimental
    Treating Opioid Patients' Pain and Sadness (TOPPS)

    TOPPS, consists of three main components: (1) psychoeducation about pain, depression, opioid use, their interactions, and the maintaining role of avoidance; (2) coaching in being an informed, activated patient (based in part on the chronic care model and on approaches to self-management of chronic illness); and (3) behavioral activation to increase engagement in meaningful activities.

    Behavioral: Treating Opioid Patients' Pain and Sadness (TOPPS)

  • Active comparator
    Health Education (HE)

    Participants randomized to the control HE condition are offered six telephone sessions led by the Behavioral Health Specialists. The first health session is around nutrition. At the remaining sessions, participants choose from a menu of topics, including: a second session on nutrition; germs, colds and the flu; preventing cancer; diabetes; protecting your heart; getting a good night's sleep; complementary and alternative medicine; caffeine, or physical activity.

    Behavioral: Health Education (HE)

Interventions

  • BehavioralTreating Opioid Patients' Pain and Sadness (TOPPS)

    TOPPS, consists of three main components: (1) psychoeducation about pain, depression, opioid use, their interactions, and the maintaining role of avoidance; (2) coaching in being an informed, activated patient (based in part on the chronic care model and on approaches to self-management of chronic illness); and (3) behavioral activation to increase engagement in meaningful activities.

  • BehavioralHealth Education (HE)

    Participants randomized to the control HE condition are offered six telephone sessions led by the Behavioral Health Specialists. The first health session is around nutrition. At the remaining sessions, participants choose from a menu of topics, including: a second session on nutrition; germs, colds and the flu; preventing cancer; diabetes; protecting your heart; getting a good night's sleep; complementary and alternative medicine; caffeine, or physical activity.

06

What researchers measure

Primary outcomes

  1. Pain Interference Based on the Brief Pain Inventory

    The Brief Pain Inventory Interference Scale (BPI-I) will be used to capture the domain of pain interference with physical and psychosocial functioning. The pain interference subscale includes 7 questions assessing the degree to which pain interferes with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life using a 0-to-10 numeric rating score. For interference items, 0 represents "does not interfere" and 10 indicates "interferes completely."

    Time frame: 3 Months

  2. Pain Severity Based on the Brief Pain Inventory

    Pain severity will be measured by the Visual Analogue Scale (VAS) presented as a 100-mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "no pain at all" and "worst pain imaginable." Participants will indicate "average" pain in the last week. Scores range between 0 and 10.

    Time frame: 3 Months

  3. Depression Based on the Patient Health Questionnaire-9

    The Patient Health Questionnaire (PHQ-9) will be used to measure depression severity and suicidality. It is the major depressive disorder module of the full PHQ. Scores range from 0-27, with scores less than or equal to 4 suggesting minimal depression, scores from 5 to 9 indicating mild depression, 10 to 14 indicating moderately depression, 15 to 19 reflecting moderately severe depression, and scores greater than 20 indicating severe depression.

    Time frame: 3 Months

Secondary outcomes

  1. Number of Participants Retained in Buprenorphine Treatment

    Using clinical records at the recruitment sites or participant self-report, we will assess whether participants were engaged in buprenorphine treatment at 12 months post study baseline

    Time frame: Month 12

07

Results

Posted Jun 26, 2025

Participant flow

Allocation
Participant flow — Allocation
MilestoneTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Started8281
Completed8281
Not completed00
Completed 3 Month Assessment
Participant flow — Completed 3 Month Assessment
MilestoneTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Started8281
Completed6065
Not completed2216
Completed 6 Month Assessment
Participant flow — Completed 6 Month Assessment
MilestoneTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Started8281
Completed6664
Not completed1617
Completed 9 Month Assessment
Participant flow — Completed 9 Month Assessment
MilestoneTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Started8281
Completed6360
Not completed1921

Outcome measures

PrimaryPain Interference Based on the Brief Pain Inventory

The Brief Pain Inventory Interference Scale (BPI-I) will be used to capture the domain of pain interference with physical and psychosocial functioning. The pain interference subscale includes 7 questions assessing the degree to which pain interferes with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life using a 0-to-10 numeric rating score. For interference items, 0 represents "does not interfere" and 10 indicates "interferes completely."

Time frame:
3 Months
Reported as:
Least squares mean · units on a scale
Pain Interference Based on the Brief Pain Inventory
units on a scaleTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Pain Interference Based on the Brief Pain Inventory5.01 (4.54 to 5.47)4.67 (4.19 to 5.47)
PrimaryPain Severity Based on the Brief Pain Inventory

Pain severity will be measured by the Visual Analogue Scale (VAS) presented as a 100-mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "no pain at all" and "worst pain imaginable." Participants will indicate "average" pain in the last week. Scores range between 0 and 10.

Time frame:
3 Months
Reported as:
Least squares mean · units on a scale
Pain Severity Based on the Brief Pain Inventory
units on a scaleTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Pain Severity Based on the Brief Pain Inventory5.17 (4.75 to 5.58)5.02 (4.65 to 5.39)
PrimaryDepression Based on the Patient Health Questionnaire-9

The Patient Health Questionnaire (PHQ-9) will be used to measure depression severity and suicidality. It is the major depressive disorder module of the full PHQ. Scores range from 0-27, with scores less than or equal to 4 suggesting minimal depression, scores from 5 to 9 indicating mild depression, 10 to 14 indicating moderately depression, 15 to 19 reflecting moderately severe depression, and scores greater than 20 indicating severe depression.

Time frame:
3 Months
Reported as:
Mean · units on a scale
Depression Based on the Patient Health Questionnaire-9
units on a scaleTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Depression Based on the Patient Health Questionnaire-910.91 (9.87 to 11.95)9.21 (8.13 to 10.30)
SecondaryNumber of Participants Retained in Buprenorphine Treatment

Using clinical records at the recruitment sites or participant self-report, we will assess whether participants were engaged in buprenorphine treatment at 12 months post study baseline

Time frame:
Month 12
Reported as:
Count of participants · Participants
Number of Participants Retained in Buprenorphine Treatment
ParticipantsTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Number of Participants Retained in Buprenorphine Treatment6361

Adverse events

Collected over Adverse event data were collected over the course of the 12-month study period.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treating Opioid Patients' Pain and Sadness (TOPPS)1/82 (1.2%)8/82 (9.8%)40/82 (48.8%)
Health Education (HE)1/81 (1.2%)15/81 (18.5%)54/81 (66.7%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
EventTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
Hospitalization- psychiatricPsychiatric disorders1/823/81
Hospitalization due to overdoseGeneral disorders1/822/81
Hospitalization due to sepsisInfections and infestations0/822/81
Hospitalization due to myocardial infarctionCardiac disorders1/822/81
Hospitalization- gallbladder removalHepatobiliary disorders0/821/81
Hospitalization due to pneumoniaInfections and infestations0/821/81
Hospitalization due to kidney stoneRenal and urinary disorders0/821/81
Hospitalization- difficulty breathingRespiratory, thoracic and mediastinal disorders0/821/81
Hospitalization due to infection in footInfections and infestations0/821/81
Hospitalization due to pneumoniaInfections and infestations1/821/81
Most frequent other events
Showing 10 of 71
Most frequent other events
EventTreating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)
FallInjury, poisoning and procedural complications6/825/81
Ear infectionInfections and infestations0/825/81
PneumoniaInfections and infestations4/822/81
Tooth abscessGastrointestinal disorders1/823/81
InfluenzaGeneral disorders1/823/81
Difficulty breathing- asthmaRespiratory, thoracic and mediastinal disorders0/823/81
Sinus infectionInfections and infestations0/823/81
MalaiseGeneral disorders0/823/81
Strep throatRespiratory, thoracic and mediastinal disorders0/823/81
Ankle sprainInjury, poisoning and procedural complications0/823/81

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
Mean45.5 ± 10.843.7 ± 10.444.6 ± 10.6
Sex: Female, Male
Sex: Female, Male(Participants)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
Female423577
Male404686
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
White6774141
African American7310
Other8412
Region of Enrollment
Region of Enrollment(participants)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
United States8281163
Pain Interference Based on the Brief Pain Inventory
Pain Interference Based on the Brief Pain Inventory(units on a scale)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
Mean6.04 ± 1.576.02 ± 1.676.03 ± 1.61
Pain Severity Based on the Brief Pain Inventory
Pain Severity Based on the Brief Pain Inventory(units on a scale)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
Mean5.68 ± 1.665.68 ± 1.665.68 ± 1.66
Patient Health Questionnaire- 9 Score
Patient Health Questionnaire- 9 Score(units on a scale)Treating Opioid Patients' Pain and Sadness (TOPPS)Health Education (HE)Total
Mean12.33 ± 5.0712.04 ± 4.9612.18 ± 5.00
08

Study locations

2 sites
  • Boston Medical Center
    Boston, Massachusetts 02118, United States
  • Stanley Street Treatment and Resources
    Fall River, Massachusetts 02720, United States
09

References and documents

Publications

  • Stein MD, Bendiks S, Karzhevsky S, Pierce C, Dunn A, Majeski A, Herman DS, Weisberg RB. Study protocol for the Treating Opioid Patients' Pain and Sadness (TOPPS) study - A randomized control trial to lower depression and chronic pain interference, and increase care retention among persons receiving buprenorphine. Contemp Clin Trials. 2024 Aug;143:107608. doi: 10.1016/j.cct.2024.107608. Epub 2024 Jun 13. PubMed 38878997 ↗
  • Haley DF, Stein MD, Bendiks S, Karzhevsky S, Pierce C, Dunn A, Herman DS, Anderson B, Weisberg RB. Associations of discomfort intolerance, discomfort avoidance, and cannabis and alcohol use among persons with chronic pain receiving prescription buprenorphine for opioid use disorder. Drug Alcohol Depend. 2024 Dec 1;265:112472. doi: 10.1016/j.drugalcdep.2024.112472. Epub 2024 Oct 24. PubMed 39488941 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 8, 2025
  • Informed consent form · Sep 24, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03698669
Lead sponsor
Boston University
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Sponsor
First posted
Oct 9, 2018
Start date
Aug 21, 2019
Primary completion
Jun 28, 2024
Completion
Dec 20, 2024
Results posted
Jun 26, 2025
Last update
Jan 8, 2026

Study contacts

Michael D Stein, MD
principal investigator · Boston University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion