Chronic Low Back Pain, Negative Affectivity
Conditions
Keywords
chronic pain, low back pain, fibromyalgia, mood, affect, depression, anxiety, opioid use
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.
Interventions
DRUGAntidepressant
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.
OTHEREnhanced Fear Avoidance Rehabilitation
The EFAR treatment utilizes standardized physical and/or occupational therapy fear avoidance approaches, including 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.
Sponsors
Ajay Wasan, MD, Msc
National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Mayo Clinic
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| "Composite Responder", Involving the Domains of Pain, Function, and Depression. See "Other Pre-Specified Outcomes" for Description of These Sub-components. | Baseline vs. 4th month of study | To create the "composite responder" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the "composite responder" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The "composite responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1. A participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. This is converted to a T score. A lower T-scores suggest better outcomes. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. 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 symptoms with 4 questions ranked on a 5-point scale, from "never" to "always". The minimum raw score is a 4 and the maximum is 20.. These are converted to a T score. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. Lower T-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. |
| Change From Baseline Sleep Disturbance 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. This is converted to a T score. Lower T scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. |
| 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). This is the percentage reporting "very much improved" or "much improved" at the end of Phase 1. We averaged their PGIC ratings in the 4th month. |
| Neuropathic Pain Symptoms Change, Baseline vs. 4 Months | Baseline vs. 4 months | Using PainDetect, we will compare changes in neuropathic pain symptoms from baseline to 4 months. PainDetect is scored from 0-38 and based on ratings to symptom items scored from '0' (never) to '5' (very strongly). Lower scores are better. |
| Fear Avoidance Beliefs, Baseline vs. 4 Months | Baseline vs. 4 months | Using the Fear Avoidance Beliefs Questionnaire, Physical Activities Items, subjects rate from '0' (completely disagree) to '6' (completely agree) five physical activities which may make their pain worse. The items are summed to produce the total score. The minimum score is a 0 and the maximum is a 30. Lower scores are better. |
| Change in PROMIS Fatigue Score From Baseline vs. 4 Months | Baseline vs. 4 months | The PROMIS short form v. 1.0 for Fatigue consists of 2 items rated from 1-5, from "not at all" to "very much." The minimum raw score is a 2 and the maximum is a 10. The raw score is summed and converted to a T score. Lower T scores are better. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. |
| Widespread Pain Index | Baseline vs. 4 months | This measure assesses the degree of widespread pain. 20 body regions are rated by patient as having pain or not. The minumum scores is a 0 and the maximum is a 20. The number of regions is summed to give the total score. Lower scores are better. |
| WPI Symptom Severity Score | Baseline to 4 months | Overall symptom severity is rated 0-10. Lower scores are better. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAjay Wasan, MD, MSc
University of Pittsburgh
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.9 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 154 Participants |
| Region of Enrollment United States | 72 participants |
| Sex: Female, Male Female | 140 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 103 | 0 / 105 |
| other Total, other adverse events | 0 / 100 | 0 / 103 | 0 / 105 |
| serious Total, serious adverse events | 12 / 100 | 7 / 103 | 5 / 105 |
Outcome results
None listed