The BEST Trial: Biomarkers for Evaluating Spine Treatments

The BEST Trial (Biomarkers for Evaluating Spine Treatments) is a NIAMS-sponsored clinical trial being conducted through the NIH 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 an algorithm for optimally assigning treatments based on an individual's phenotypic markers and response to 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.

The secondary objectives are to (a) estimate Dynamic Treatment Regimes (DTRs) that optimally balance multiple outcomes, taking into account participant preferences for outcomes including pain intensity, pain interference, physical function, opioid use, depression, anxiety, sleep duration and sleep disturbance, (b) estimate DTRs that incorporate additional phenotypic markers (i.e., deep phenotyping) collected on a sub-set of participants, and (c) assess whether effectiveness is sustained based on outcomes collected 24 weeks after randomization to the second treatment.