Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain
Overview
- Phase
- Phase 2
- Intervention
- Antidepressant
- Conditions
- Chronic Low Back Pain
- Sponsor
- Ajay Wasan, MD, Msc
- Enrollment
- 308
- Locations
- 3
- Primary Endpoint
- "Composite Responder", involving the domains of pain, function, and depression. See "Other Pre-Specified Outcomes" for description of these sub-components.
- Status
- Completed
- Last Updated
- 3 months ago
Overview
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.
Investigators
Ajay Wasan, MD, Msc
Professor
University of Pittsburgh
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
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
Arms & Interventions
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.
Intervention: Antidepressant
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.
Intervention: Enhanced Fear Avoidance Rehabilitation
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.
Intervention: Antidepressant
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.
Intervention: Enhanced Fear Avoidance Rehabilitation
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.
Intervention: Antidepressant
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.
Intervention: Enhanced Fear Avoidance Rehabilitation
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.
Intervention: Antidepressant
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.
Intervention: Enhanced Fear Avoidance Rehabilitation
Outcomes
Primary Outcomes
"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 will form a "combined responder" metric, and the response rate to depression will be measured as well. 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. "Combined response" and "depression response" will be integrated to determine the "composite responder" rate. A participant could be a combined 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 combined responders (pain+function measure) and the rate of depression responders (other pre-specified outcomes).
Secondary Outcomes
- Change from Baseline Anxiety at 4 months using PROMIS(Baseline vs. 4 months)
- Widespread Pain Index(Baseline vs. 4 months)
- Change from Baseline Pain Interference at 4 months using PROMIS(Baseline vs. 4 months)
- Neuropathic pain symptoms change, baseline vs. 4 months(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)
- Change in PROMIS Fatigue score from baseline vs. 4 months(Baseline vs. 4 months)
- Fear avoidance beliefs, baseline vs. 4 months(Baseline vs. 4 months)