Treating Negative Affect in Low Back Pain Patients (TNA-LBP)

Ajay Wasan, MD, Msc

Status and phase: Completed; Phase 3; Phase 2

Conditions: Chronic Low Back Pain; Negative Affectivity

Treatments: Other: Enhanced Fear Avoidance Rehabilitation; Drug: Antidepressant

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04747314

UG3AR076568 (U.S. NIH Grant/Contract)

STUDY21010105

Details and patient eligibility

About

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.

Full 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.

Enrollment: 308 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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308 participants in 5 patient groups

Antidepressant (AD)

Experimental group

Description:

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.

Treatment:

Drug: Antidepressant

Enhanced Fear Avoidance Rehabilitation (EFAR)

Experimental group

Description:

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.

Treatment:

Other: Enhanced Fear Avoidance Rehabilitation

Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)

Experimental group

Description:

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.

Treatment:

Drug: Antidepressant

Other: Enhanced Fear Avoidance Rehabilitation

AD -> EFAR

Experimental group

Description:

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.

Treatment:

Drug: Antidepressant

Other: Enhanced Fear Avoidance Rehabilitation

EFAR -> AD

Experimental group

Description:

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.

Treatment:

Drug: Antidepressant

Other: Enhanced Fear Avoidance Rehabilitation