Treating Negative Affect in Low Back Pain Patients

NCT04747314 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY21010105UG3AR076568
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Low Back Pain; Negative Affectivity

Keywords

chronic pain; low back pain; fibromyalgia; mood; affect; depression; anxiety; opioid use

Outcome Measures

Primary Outcomes (1)

• "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

Secondary Outcomes (8)

• Change from Baseline Pain Interference at 4 months using PROMIS

  Baseline vs. 4 months

• Change from Baseline Anxiety at 4 months using PROMIS

  Baseline vs. 4 months

• Change from Baseline Sleep Disturbance at 4 months using PROMIS

  Baseline vs. 4 months

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

  Baseline vs. 4 months

• Neuropathic pain symptoms change, baseline vs. 4 months

  Baseline vs. 4 months

Other Outcomes (3)

• 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.

  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.

  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.

  Baseline vs. 4 months

Study Arms (5)

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.

Drug: Antidepressant

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.

Other: Enhanced Fear Avoidance Rehabilitation

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.

Drug: Antidepressant; Other: Enhanced Fear Avoidance Rehabilitation

AD -> EFAR

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. 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; Other: Enhanced Fear Avoidance Rehabilitation

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.

Drug: Antidepressant; Other: Enhanced Fear Avoidance Rehabilitation

Interventions

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.

Also known as: AD: aripiprazole, bupropion, duloxetine, escitalopram, mirtazapine, sertraline, venlafaxine

AD -> EFAR; Antidepressant (AD); Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR); EFAR -> AD

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.

Also known as: EFAR

AD -> EFAR; Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR); EFAR -> AD; Enhanced Fear Avoidance Rehabilitation (EFAR)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: collaborator
• Massachusetts General Hospital: collaborator
• Ajay Wasan, MD, Msc: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (3)

BWH Pain Management Center

Chestnut Hill, Massachusetts, 02467, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

UPMC Pain Medicine At Centre Commons

Pittsburgh, Pennsylvania, 15206, United States

Location

Related Publications (1)

• 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.

  PMID: 36715655 DERIVED

MeSH Terms

Conditions

Chronic Pain; Low Back Pain; Fibromyalgia; Depression; Anxiety Disorders

Interventions

Antidepressive Agents; Bupropion; Duloxetine Hydrochloride; Escitalopram; Mirtazapine; Sertraline; Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Back Pain; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Behavioral Symptoms; Behavior; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Propiophenones; Ketones; Organic Chemicals; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dibenzazepines; Heterocyclic Compounds, 3-Ring; 1-Naphthylamine; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Lipids

Study Officials

• Ajay Wasan, MD, MSc

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: February 10, 2021
• Study Start: March 31, 2021
• Primary Completion: November 4, 2024
• Study Completion: December 20, 2024
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)