The BEST Trial (Biomarkers for Evaluating Spine Treatments) is a National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)-sponsored clinical trial being conducted through the NIH Helping to End Addiction Long-term (HEAL) Initiative's Back Pain Consortium (BACPAC) Research Program. The primary objective of this trial is to inform a precision medicine approach to the treatment of Chronic Low-Back Pain by estimating the optimal treatment or combination of treatments based on patient features and response to the initial treatment. Interventions being evaluated in this trial are: (1) enhanced self-care (ESC), (2) acceptance and commitment therapy (ACT), (3) evidence-based exercise and manual therapy (EBEM), and (4) duloxetine.
Each participant will complete an initial screening call and enrollment visit, followed by a 2-week run-in period, two consecutive 12-week treatment periods, and a 12-week post-treatment follow-up period. Upon completion of the run-in period, participant eligibility will be reassessed based on adherence to study protocol. Participants who no longer meet eligibility criteria will be considered screen failures and discontinued from the study. All participants will undergo phenotyping assessments at Visit 0, 1 and 2 corresponding to baseline, the end of the first 12-week intervention period, and the end of the second 12-week intervention period, respectively. A subset of participants will undergo additional phenotyping, consisting of a more comprehensive set of phenotyping assessments, at the same visits. Pain, Enjoyment of Life, and General Activity (PEG) and Patient Global Impressions Scale (PGIC) will be assessed at 6 weeks (midpoint of intervention period one), 12 weeks (Visit 1), 18 weeks (midpoint of intervention period two), 24 weeks (Visit 2), and 36 weeks post-baseline (12 weeks after intervention period two). Basic safety assessments will also be performed at these time points to assess participant tolerability to their current study intervention(s). Patients who are unable to tolerate their assigned study treatment will be educated on how to safely discontinue their current treatment plan but will otherwise remain in the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
1,014
The Enhanced Self-Care intervention will be comprised of educational modules on evidence-based cognitive-behavioral self-management skills for pain. These modules will be provided digitally for self-administration over a period of 12 weeks. There will be no therapist associated with the delivery of these educational materials; however, after the first four modules, email or text messages will be used to make personalized recommendations for accessing additional modules based upon identified problems from the baseline assessment. Additionally, the walking program module will utilize Fitbit step tracking to allow participants to monitor their walking progress.
ACT is a form of cognitive behavioral therapy that is well established for the treatment of chronic pain. The goal of ACT is to build psychological flexibility thereby interrupting pain avoidance behavior patterns. Participants randomized to ACT will take part in 12 sessions over the course of 12 weeks. Sessions will be delivered as a combination of 4 remote face-to-face visits with a therapist and 8 therapist-supported online sessions (self-directed online modules supported by provider coaching). Online sessions will focus on helping participants accept pain, connect with negative thoughts and emotions, develop mindfulness and identify and commit to values and goals that are important to them. During face-to-face sessions with the therapist, participants will be encouraged to share their experience of skills practice and mastery, provide examples of skill use at home, and describe what barriers they encountered.
Licensed physical therapists (PTs) or Doctors of Chiropractic (DCs) will rely on evidence-based guidance to direct decision-making on the particular type of manual and exercise therapy that may be best suited to an individual study participant. Special attention will be paid to the clinician's choice of language in regard to the purpose and expected outcomes of manual therapy in order to avoid enhancing catastrophizing ideations or preference for passive interventions. A total of 10 sessions will be provided over an 8-week treatment period. Two sessions per week are provided in the first two weeks followed by weekly sessions over the next 6 weeks. Treatment sessions will last approximately 60 minutes each.
Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for use in Chronic Low-Back Pain, and, as such, is included as a recommended therapy in nearly all current treatment guidelines for low back pain. Study participants will be treated with duloxetine for 12 weeks during the active treatment phase. At the time of randomization, the approved drug pharmacy at each study site will dispense between 185 and 192 duloxetine 30 mg capsules and provide to participants. This will ensure enough capsules to maintain up to a 60 mg dosage through the 12-week intervention phase and to taper the dose in the 13th week if needed.
Stanford University
Redwood City, California, United States
University of California, San Diego
San Diego, California, United States
University of California, San Francisco
San Francisco, California, United States
University of Kansas Health System
Kansas City, Kansas, United States
Massachusetts General Hospital/Brigham Women's Hospital, Harvard Medical School
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
University of North Carolina Hospital Pain Management Clinic
Chapel Hill, North Carolina, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
...and 2 more locations
Patient-Reported Pain Intensity and Interference Score
Patient-reported pain intensity and interference is measured by the Pain, Enjoyment of Life, and General Activity (PEG) scale. The PEG is a series of 3 questions. Results range from -10 to 10, with higher scores indicating increased pain intensity and interference at 24 Weeks compared to Baseline.
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System-Pain Interference
Pain interference is measured by the 4-item PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference scale (PROMIS-PI, 4a). The PROMIS-PI, 4a is a series of 4 questions, and measures self-reported consequences of pain on relevant aspects of one's life. Results range from -34 to 34 (t-scores range from 41.6 to 75.6). For each t-score, 50 indicates the population mean with a standard deviation of 10. Lower scores indicate lower pain interference and a better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Time frame: Baseline, 24 Weeks
Number of Participants Self-Reporting Taking Opioids
The number of participants self-reporting taking opioids ("Yes" response) is measured by a single question, "Are you currently taking any opioid pain medication on a daily basis?".
Time frame: 24 Weeks
Patient-Reported Outcomes Measurement Information System- Physical Function
Physical function is measured by the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) Short Form 6b. The PROMIS-PF Short Form 6b is a series of 6 questions. T-scores range from 21.6 to 58.7 and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -37.1 to 37.1, with higher physical function scores indicating a better outcome and increased physical functioning at 24 Weeks compared to Baseline. A higher physical function is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Score
Depression score is measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) 4-item depression scale from the PROMIS 29 profile. The PROMIS 4-item depression scale from the PROMIS 29 profile is a series of 4 questions. T-scores range from 41.0 to 79.4), and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -38.4 to 38.4, with higher scores indicating increased depression at 24 Weeks compared to Baseline. A lower depression score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety
Anxiety score is measured by the Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety (PROMIS-EDA) scale 4a. The PROMIS-EDA 4a is a series of 4 questions. T-scores range from 40.3 to 81.6, and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -41.3 to 41.3, with higher scores indicating increased anxiety at 24 Weeks compared to Baseline. A lower anxiety score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System - Sleep Disturbance
Sleep disturbance is measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) short form 6a. The PROMIS short form 6a is a series of 6 questions. T-scores range from 31.7 to 76.1 and for each t-score, 50 indicates the population mean with a standard deviation of 10). Results range from -44.4 to 44.4, with higher scores indicating increased sleep disturbance at 24 Weeks compared to Baseline. A lower sleep disturbance score is the better outcome. PPROMIS measures are not used for clinical decision making but to describe participant symptoms.
Time frame: Baseline, 24 Weeks
Sleep Duration
Sleep duration is measured by the Back Pain Consortium (BACPAC) sleep duration question, "During the past month, how many hours and minutes of actual sleep did you get at night? (This may be different than the number of hours and minutes you spent in bed)." Participants respond with a number of hours and minutes. Results range from -24 to 24 hours, with higher number of hours indicating increased sleep duration at 24 Weeks compared to Baseline.
Time frame: Baseline, 24 Weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.