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| ID | Type | Description | Link |
|---|---|---|---|
| UG3AR076568 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
| Mayo Clinic | OTHER |
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This study will examine how the use of antidepressant, physical therapy, and combination of both affects pain, function, and depression outcomes in chronic low back pain patients.
Approximately 20 million Americans are affected by chronic low back pain and negative affective states such as depression and anxiety. These negative states have all been associated with higher pain intensity, lower pain tolerance, greater use of pain medication, poor pain treatment responses, and higher levels of psychiatric comorbidity among low back pain patients. To improve these outcomes for those who suffer from low back pain, it is important to implement multiple methods with a focus in treating negative affect for pain management rather than using opioids alone.
Antidepressant (AD) and fear avoidance-based physical therapy (EFAR) have individually shown to be promising methods for pain management. In this study, AD, EFAR, and the combination therapy of the two treatments will be explored and implemented to investigate their effectiveness in improving pain, function, depression, and anxiety. The key innovation is testing a new and effective multimodal treatment that can help manage pain, as well as address negative affect.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Antidepressant (AD) | Experimental | Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months. |
|
| Enhanced Fear Avoidance Rehabilitation (EFAR) | Experimental | Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months. |
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| Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR) | Experimental | Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group. |
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| AD -> EFAR | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antidepressant | Drug | The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes. The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change. |
| Measure | Description | Time Frame |
|---|---|---|
| "Composite Responder", involving the domains of pain, function, and depression. See "Other Pre-Specified Outcomes" for description of these sub-components. | To create the "composite responder" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component. This is done to simplify the assessment of multi-domain responses. We took this "composite responder" approach since pain, function and depression are inherently related to each other in this patient group with CLBP and high negative affect. "Pain+function" and "depression response" will be integrated to determine the "composite responder" rate. A participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining response vs. non-response to each domain. The primary outcome is the rate of response vs. non-response on the "Composite Responder" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes). | Baseline vs. 4th month of study |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline Pain Interference at 4 months using PROMIS | The PROMIS Short Form v1.1 - Pain Interference 4a will assess self-reported consequences of pain with 4 questions ranked on a 5-point scale, from "not at all" to "very much". The minimum raw summed score is 4 and the maximum score is 20. Lower t-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Physical Function using PROMIS Short Form 2.0. Function is part of the Composite Responder measure, and a pain+function metric more specifically. A subject could be a pain+function responder, a depression responder, both, or neither. | The PROMIS Short Form v2.0 - Physical Function 6b questionnaire will assess self-reported capability with 6 qualitatively scaled questions ranked on a 5-point scale, from "without any difficulty" to "unable to do" or "not at all" to "cannot do." The minimum raw summed score is 6 and the maximum score is 30. Lower t-scores suggest better outcomes. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajay Wasan, MD, MSc | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BWH Pain Management Center | Chestnut Hill | Massachusetts | 02467 | United States | ||
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36715655 | Derived | Wasan AD, Edwards RR, Kraemer KL, Jeong J, Kenney M, Luong K, Cornelius MC, Mickles C, Dharmaraj B, Sharif E, Stoltenberg A, Emerick T, Karp JF, Bair MJ, George SZ, Hooten WM. Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect. Pain Med. 2023 Aug 4;24(Suppl 1):S105-S114. doi: 10.1093/pm/pnad006. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Sep 3, 2024 | Mar 4, 2025 | ICF_000.pdf |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Apr 20, 2026 | May 11, 2026 | 13 | ||
| Jun 6, 2026 |
| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| D017116 | Low Back Pain |
| D005356 | Fibromyalgia |
| D003863 | Depression |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000928 | Antidepressive Agents |
| D016642 | Bupropion |
| D000068736 | Duloxetine Hydrochloride |
| D000089983 | Escitalopram |
| D000078785 | Mirtazapine |
| D020280 | Sertraline |
| D000069470 | Venlafaxine Hydrochloride |
| ID | Term |
|---|---|
| D011619 | Psychotropic Drugs |
| D002491 | Central Nervous System Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
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| Massachusetts General Hospital |
| OTHER |
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Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks.
Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months. Those re-randomized to receive EFAR for another 4 months will receive a combination of antidepressant medication and physical therapy, in addition to their current opioid prescription and weaning guidelines, if applicable.
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| EFAR -> AD | Experimental | Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months. Those re-randomized to receive AD for another 4 months will be under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. |
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| Enhanced Fear Avoidance Rehabilitation | Other | The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes. |
|
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| Baseline vs. 4 months |
| Change from Baseline Anxiety at 4 months using PROMIS | The PROMIS Short Form v1.0 - Anxiety 4a will assess self-reported fear, anxious misery, hyperarousal, and somatic symptoms with 4 questions ranked on a 5-point scale, from "never" to "always". The minimum raw summed score is 4 and the maximum score is 20. Lower t-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. | Baseline vs. 4 months |
| Change from Baseline Sleep Disturbance at 4 months using PROMIS | The PROMIS Short Form v1.0 - Sleep Disturbance 6a self-reported perceptions of sleep quality and sleep depth with 6 questions ranked on a 5-point scale. The minimum raw summed score is 6 and the maximum score is 30. Lower t-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. | Baseline vs. 4 months |
| Change from Baseline Subject's Perception of Change from Treatment at 4 months using Patient Global Impression of Change (PGIC) | The subject's impression of the impact of the treatment on their pain and function will be measured with a 7-item scale (1 = very much worse, 2 = much worse, 3 = minimally worse, 4 = no change, 5 = minimally improved, 6 = much improved, 7 = very much improved). | Baseline vs. 4 months |
| Neuropathic pain symptoms change, baseline vs. 4 months | Using PainDetect, we will compare changes in neuropathic pain symptoms from baseline to 4 months. PainDetect is scored from 0-38 and based on ratings to symptom items scored from '0' (never) to '5' (very strongly). | Baseline vs. 4 months |
| Fear avoidance beliefs, baseline vs. 4 months | Using the Fear Avoidance Beliefs Questionnaire, Physical Activities Items, subjects rate from '0' (completely disagree) to '6' (completely agree) four physical activities which may make their pain worse. The items are summed to produce the total score. | Baseline vs. 4 months |
| Widespread Pain Index | This measure assesses the degree of widespread pain. 20 body regions are rated by patient as having pain or not. The number of regions is summed to give the total score. | Baseline vs. 4 months |
| Change in PROMIS Fatigue score from baseline vs. 4 months | The PROMIS short form v. 1.0 for Fatigue consists of 2 items rated from 1-5, from "not at all" to "very much." The raw score is summed and converted to a T score. | Baseline vs. 4 months |
| Baseline vs. 4 months |
| Change in Pain Intensity using PROMIS. Pain is part of the Composite Responder measure, and a pain+function metric more specifically. A subject could be a pain+function responder, a depression responder, both, or neither. | The PROMIS Numeric Rating Scale v1.0 for average pain intensity-- Pain Intensity 1a questionnaire will assess how much a person hurts on average over the past 7 days, with a question ranked on a 11-point scale, from "0 = no pain" to "10 = worst imaginable pain." The minimum raw summed score is 0 and the maximum score is 10. Lower raw response scores suggest lower pain intensity and better outcomes. | Baseline vs. 4 months |
| Change in Depression using PROMIS. Depression is part of the "Composite Responder" measure. A subject could be a pain+function responder, a depression responder, both, or neither. | The PROMIS Short Form v1.0 - Depression 4a will assess self-reported negative mood and views of self with 4 questions ranked on a 5-point scale, from "never" to "always". The minimum raw summed score is 4 and the maximum score is 20. Lower t-scores suggest better outcomes. | Baseline vs. 4 months |
| Rochester |
| Minnesota |
| 55905 |
| United States |
| UPMC Pain Medicine At Centre Commons | Pittsburgh | Pennsylvania | 15206 | United States |
| Jul 1, 2026 |
| 14 |
| D001416 | Back Pain |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D001523 | Mental Disorders |
| D020164 | Chemical Actions and Uses |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011437 | Propylamines |
| D000588 | Amines |
| D009570 | Nitriles |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D015057 | 1-Naphthylamine |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D008055 | Lipids |