TNA-LBP: Treating Negative Affect in Low Back Pain Patients

Sponsor

Ajay Wasan, MD, Msc (Other)

Overall Status

Recruiting

CT.gov ID

NCT04747314

Collaborator

National Institutes of Health (NIH) (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), Brigham and Women's Hospital (Other), Mayo Clinic (Other)

300

Enrollment

Locations

Arms

Anticipated Duration (Months)

100

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Low Back Pain Negative Affectivity	Drug: Antidepressant Other: Enhanced Fear Avoidance Rehabilitation	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 31, 2021

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Apr 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Antidepressant (AD) 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.	Drug: Antidepressant 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
Experimental: Enhanced Fear Avoidance Rehabilitation (EFAR) 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.	Other: Enhanced Fear Avoidance Rehabilitation 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
Experimental: Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR) 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.	Drug: Antidepressant 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 Other: Enhanced Fear Avoidance Rehabilitation 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
Experimental: AD -> EFAR 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.	Drug: Antidepressant 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 Other: Enhanced Fear Avoidance Rehabilitation 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
Experimental: EFAR -> AD 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.	Drug: Antidepressant 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 Other: Enhanced Fear Avoidance Rehabilitation 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

Outcome Measures

Primary Outcome Measures

Change from Baseline Physical Function at 4 months using PROMIS [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.
Change from Baseline Pain Intensity at 4 months using PROMIS [Baseline vs. 4 months]
The PROMIS Numeric Rating Scale v1.0 - Pain Intensity 1a questionnaire will assess how much a person hurts 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.
Change from Baseline Depression at 4 months using PROMIS [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. Outcomes will be measured and compared between the 3 treatment groups.

Secondary Outcome Measures

Change from Baseline Pain Interference at 4 months using PROMIS [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.
Change from Baseline Anxiety at 4 months using PROMIS [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.
Change from Baseline Sleep at 4 months using PROMIS [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.
Change from Baseline Opioid Cravings at 4 months using the Craving Index [Baseline vs. 4 months]
The Craving Index questionnaire will assess opioid cravings with 4 questions ranked on a 0-10 scale, from "0 = not at all" to the "10 = strong as possible." Lower scores suggest lower craving.
Change from Baseline Subject's Perception of Change from Treatment at 4 months using Patient Global Impression of Change (PGIC) [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).
Change from Baseline Opioid Misuse at 4 months using Current Opioid Misuse Measure [Baseline vs. 4 months]
The Current Opioid Misuse Measure (COMM) questionnaire will assess recent feelings and behaviors with 17 questions ranked on a 5-point scale, from "never" to "very often". The minimum raw summed score is 0 and the maximum score is 68. Lower scores suggest little to no opioid misuse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Evidence of a prior lumbar spine X-ray to rule out red flags, such as infection, tumor, or fracture
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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BWH Pain Management Center	Chestnut Hill	Massachusetts	United States	02467
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	UPMC Pain Medicine At Centre Commons	Pittsburgh	Pennsylvania	United States	15206