Treating Negative Affect in Low Back Pain Patients

NCT ID: NCT04747314

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 308 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-31
• Study Completion Date: 2024-12-20

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.

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.

Conditions

Chronic Low Back Pain; Negative Affectivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Antidepressant

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Enhanced Fear Avoidance Rehabilitation

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Antidepressant

Intervention Type: 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.

Enhanced Fear Avoidance Rehabilitation

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Antidepressant

Intervention Type: 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.

Enhanced Fear Avoidance Rehabilitation

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Antidepressant

Intervention Type: 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.

Enhanced Fear Avoidance Rehabilitation

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

AD: aripiprazole, bupropion, duloxetine, escitalopram, mirtazapine, sertraline, venlafaxine; EFAR

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Ajay Wasan, MD, Msc

OTHER

Sponsor Role: lead

Responsible Party

Ajay Wasan, MD, Msc

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ajay Wasan, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

BWH Pain Management Center

Chestnut Hill, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

UPMC Pain Medicine At Centre Commons

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36715655 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

UG3AR076568

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY21010105

Identifier Type: -

Identifier Source: org_study_id