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Completed

NCT Number: NCT04747314

Treating Negative Affect in Low Back Pain Patients

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.

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Key information

Conditions

Chronic Low Back Pain Anxiety Disorders Back Pain Behavior Behavioral Symptoms Chronic Pain Depression Fibromyalgia Low Back Pain Mental Disorders Muscular Diseases Musculoskeletal Diseases Negative Affectivity Nervous System Diseases Neurologic Manifestations Neuromuscular Diseases Pain Pathological Conditions, Signs and Symptoms Rheumatic Diseases Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

BWH Pain Management Center, Chestnut Hill, Massachusetts, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Ages 18-75
  • Pain duration > 6 months
  • Must meet the minimum criteria for cognitive function using the PROMIS 2-item cognitive screener (>3)
  • Average pain score of > 3/10, with low back pain being the primary pain site
  • CLBP meeting Quebec Task Force Classification System categories I-III (from axial pain only to pain radiating beyond the knee without neurological signs). Constant radicular pain associated with sensory loss is highly treatment resistant without surgery
  • In the investigator's judgment, evidence of healthcare seeking for low back pain.
  • Must meet criteria for high negative affect at 1st study visit: at least 5 on the PHQ-4 (also called the PHQ-2 + GAD-2). Scores above this level are highly associated with having a co-morbid major depression or generalized anxiety disorder diagnosis PHQ-4 scores are used as a proxy for high scores on PROMIS depression and anxiety scales
  • Having accessible electronic medical records from UPMC, Brigham and Women's Hospital, or Mayo Clinic, Rochester.
  • For those taking opioids (the opioid subgroup), participants must be prescribed opioids currently for at least 3 consecutive months prior to enrollment. Patients must be on opioids for a minimum of three months, taking them on a daily basis or intermittently during the week. The investigators will include those on strong opioids, such as oxycodone and weak opioids, such as tramadol.
  • Subject must agree that opioids cannot be increased during the study
  • For those taking opioids, no active substance use disorder in the past year as determined by the PI with the use of the Tobacco, Alcohol, Prescription Medications, and Other Substance Tool (TAPS) and a urine toxicology screen. The exceptions are tobacco, medical marijuana use in Pennsylvania or Minnesota, recreational or medical marijuana in the Boston site, or mild prescription opioid use disorder such as opioid misuse
  • No acute suicidality or history of major thought disorder (such as mania or psychosis). This will be assessed at study entry which will also include a review of history in EPIC/EMR
  • Must possess a mobile device or tablet that can send and receive text messages and access the internet

Exclusion criteria

  • Back surgery within the past six months
  • Active worker's compensation or litigation claims
  • New pain and/or psychiatric treatments within 2 weeks of enrollment
  • Intent to add new or increase pain treatments during the study period, such as back surgery, nerve block procedures, or medications
  • Intent to add new psychiatric treatments during the first 4 months of the study
  • Any clinically unstable systemic illness that is judged to interfere with the trial
  • History of cardiac, nervous system, or respiratory disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for respiratory depression
  • Non-ambulatory status
  • Pregnancy or the intent to become pregnant during the study. Women of childbearing potential will all submit a urine sample pregnancy testing at enrollment.
  • Not fluent in English and/or not able to complete the questionnaires

Treatment and study plan

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.

Other names: AD: aripiprazole, bupropion, duloxetine, escitalopram, mirtazapine, sertraline, venlafaxine

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.

Other names: EFAR

Primary outcomes

  1. "Composite Responder", involving the domains of pain, function, and depression. See "Other Pre-Specified Outcomes" for description of these sub-components.

    Time frame: Baseline vs. 4th month of study

    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).

Secondary outcomes

  1. Change from Baseline Pain Interference at 4 months using PROMIS

    Time frame: Baseline vs. 4 months

    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.

  2. Change from Baseline Anxiety at 4 months using PROMIS

    Time frame: Baseline vs. 4 months

    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.

  3. Change from Baseline Sleep Disturbance at 4 months using PROMIS

    Time frame: Baseline vs. 4 months

    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.

  4. Change from Baseline Subject's Perception of Change from Treatment at 4 months using Patient Global Impression of Change (PGIC)

    Time frame: Baseline vs. 4 months

    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).

  5. Neuropathic pain symptoms change, baseline vs. 4 months

    Time frame: 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).

  6. Fear avoidance beliefs, baseline vs. 4 months

    Time frame: 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.

  7. Widespread Pain Index

    Time frame: Baseline vs. 4 months

    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.

  8. Change in PROMIS Fatigue score from baseline vs. 4 months

    Time frame: 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.

Other outcomes

  1. 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.

    Time frame: Baseline vs. 4 months

    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.

  2. 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.

    Time frame: Baseline vs. 4 months

    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.

  3. 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.

    Time frame: Baseline vs. 4 months

    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.

Sponsors and collaborators

Lead sponsor

Ajay Wasan, MD, Msc

Other

Collaborators

  • Massachusetts General Hospital
  • Mayo Clinic
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • National Institutes of Health (NIH)

Registry information

Official study title

Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain

Acronym: TNA-LBP

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Feb 10, 2021
Registry last updated
Jan 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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