Strategies to Assist With Management of Pain

Chronic low back pain (CLBP) is the most common disabling chronic noncancer pain condition
treated with opioids. Many opioid-treated patients experience inadequate pain relief and
disability as well as dose-dependent adverse effects of opioids, such as worse mental health,
opioid misuse, overdose and death. They frequently have co-occurring depression, anxiety, and
opioid use disorders, which worsen outcomes. Poor outcomes and opioid-related harms
underscore the need for safe and effective strategies for chronic pain care and opioid dose
reduction, especially in high-impact, opioid-treated pain, as noted by the Institute of
Medicine, the National Institutes of Health, and the Patient-Centered Outcomes Research
Institute.

Our pilot randomized controlled trial (RCT) of mindfulness meditation (MM), a popular
mind-body modality, demonstrated its potential to safely improve the health of patients and
reduce opioid dosage in opioid-treated CLBP. To expand the evidence for MM for use in
opioid-treated chronic pain, the Investigators propose a 5-year multi-site, mixed-methods
pragmatic RCT comparing the effectiveness of MM to standard-of-care cognitive behavioral
therapy (CBT) for improving outcomes in opioid-treated CLBP. The study team will follow 766
participants over 12 months and compare outcomes that matter to patients and their families
in 383 adults randomized to the MM group to 383 adults randomized to the CBT group,
controlling for relevant factors.

The specific aims of this study are:

1. To compare the effectiveness of MM to CBT for reducing pain and increasing function. We
hypothesize that adults with opioid-treated CLBP in the MM group will report a greater
reduction in pain severity and a greater increase in function at 6 and 12 months
compared to those in the CBT group.

2. To compare the effectiveness of MM to CBT for improving quality of life (QoL) and
reducing daily opioid dose. We hypothesize that adults with opioid-treated CLBP in the
MM group will report a greater improvement in QoL and a greater decrease in daily opioid
dose at 6 and 12 months compared to those in the CBT group.

3. To examine if participant baseline characteristics impact treatment response to MM or
CBT. We hypothesize that among those with increased baseline symptom severity of
anxiety, depression and opioid misuse behaviors, MM will be more beneficial than CBT for
improving Aim 1 and Aim 2 outcomes.

Both MM and CBT interventions are patterned after established programs, adapted to meet the
needs of patients with opioid-treated CLBP, with input from content experts and patient
partners. The manualized interventions will be delivered by trained therapists over 8 weeks
in weekly two-hour group sessions in addition to care the participants are already receiving
from their regular clinicians; participants will also be asked to practice MM or CBT
strategies at home during the entire study (at least 30 minutes/day, 6 days/week).

Eligibility criteria will focus on English-speaking adults ≥21 years old, with
moderate-to-severe CLBP treated with ≥30 mg/day of morphine-equivalent opioid dose for ≥3
months. The study will implement a limited set of exclusionary criteria to ensure a diverse
sample, from which findings can be generalized.

Outcome measures were selected and prioritized based on guidelines and stakeholder input.
They will be collected at baseline, at 3, 6, 9 and 12 months. Only baseline and 12 months
post-entry data collection will be conducted in person; the 3, 6, and 9-month data collection
will occur online or by phone to minimize burden. Pain severity and function, as assessed by
standard, validated survey measures, will serve as primary (Aim 1), and quality of life and
opioid dose (morphine-equivalent mg/day) as secondary (Aim 2) outcomes. Severity of negative
affect (depression, anxiety) and opioid misuse behaviors, also measured by validated surveys,
are the main hypothesized predictors of treatment success (Aim 3). The repeated measures
intention-to-treat outcome analysis will compare the change in primary and secondary outcomes
over the 12 month period and across the two groups. To determine prognostic factors of
treatment effect, a linear mixed model analysis will be performed for Aim 1 and Aim 2
outcomes, adjusting for potential confounders, study site and a random intercept for subject.

A team of experienced investigators and engaged stakeholders will carry out this multi-health
system, multi-site study led by the faculty from the University of Wisconsin (Madison, WI),
Harvard Medical School (Boston, MA) and the University of Utah (Salt Lake City, UT).
Stakeholders helped develop this proposal and will be integrally involved as partners in all
aspects of the study, from finalizing the methods, trouble-shooting implementation of the
research plan, and dissemination of results.

Positive findings of this study could help improve health outcomes and reduce daily opioid
dose in patients with opioid-treated CLBP, and inform clinical decisions of patients and
clinicians about the choice between MM and CBT for opioid-treated CLBP.

Inclusion Criteria (per self-report): English-speaking; age ≥ 21 years old; chronic low
back pain (defined as a pain in lumbosacral region or sciatica for ≥3 months), with an
average daily back pain score ≥3 on a 0-10 numerical rating scale (question from the Brief
Pain Inventory), treated with ≥30 mg/day of morphine-equivalent dose for ≥3 months; at
least moderate CLBP-related disability (≥21 score on the Oswestry Disability Index);
capable of giving informed consent; willing to complete the study activities.

Exclusion Criteria (per self-report): prior formal Mindfulness Meditation or Cognitive
Behavioral Therapy training; current pregnancy; diagnosis of borderline personality,
delusional, or bipolar (mania) disorder; inability to safely or reliably participate in the
study.