Clinical trial NCT03115359: Strategies to Assist With Management of Pain
Official title: A Comparative Effectiveness Randomized Controlled Trial of Mindfulness Meditation Versus Cognitive Behavioral Therapy for Opioid-Treated Chronic Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Low Back Pain
Keywords: Chronic Low Back Pain
Opioid Therapy
Chronic Pain
Mindfulness Meditation
Cognitive Behavioral Therapy
Opioid-treated Chronic Low Back Pain
CLBP
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2017-04-14
Enrollment: 770
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparative effectiveness randomized controlled trial of two behavioral interventions
Primary purpose: TREATMENT

Brief summary: Chronic low back pain (CLBP) has no known effective treatment. While often treated with long-term opioid therapy, opioids do not work well for many patients and can cause serious side effects, including addiction, poorer mental health, and overdose death. Even when paired with a standard-of-care cognitive behavioral therapy (CBT), results are limited. Patients, families and clinicians are very interested in using alternative treatments for CLBP, especially complementary and integrative treatments such as mindfulness meditation (MM). MM helps train the mind to bring non-judgmental and accepting attention to present-moment experiences such as pain. MM offers an active and safe self-care approach to chronic pain that contrasts with the passive and potentially harmful nature of opioid treatment, and may prove more effective than CBT in helping improve health and well-being, and reduce reliance on opioids in adults with opioid-treated CLBP. Although this hypothesis is supported by early research, including a pilot study by the Principal Investigator, evidence on MM's effectiveness in this population is inconclusive, presenting a critical knowledge gap.

With input from patients, family members, and clinicians, the Investigators have designed a study to address this gap and propose a clinical trial that will compare the effectiveness of MM to standard-of-care CBT in opioid-treated CLBP. Based on the existing research, it is hypothesized that MM training will lead to a larger reduction in pain intensity, increase in physical function, improvement in quality of life, and decrease in daily opioid dose, as compared to CBT training, with benefits of MM especially notable in adults with worse mood, anxiety or unhealthy opioid-use behaviors who often experience more severe symptoms of CLBP and less improvement in response to existing therapies.

To test these hypotheses, 766 adults with opioid-treated CLBP will be randomly assigned into one of two 8-week treatment groups: MM (383 participants) that will receive the MM training or CBT (383 participants) that will receive the CBT training. Due to the COVID-19 pandemic-related restrictions, the study protocol was modified in October 2020 so that the study can be completed virtually.

The effectiveness of MM versus CBT will be assessed over a 12-month period with patient-reported measures, recommended by experts and endorsed by our stakeholder partners, including patients with opioid-treated CLBP, their families and clinicians.

Detailed description: 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.

The investigators 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. Current study is based on hypothesis 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. Study team 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. Study team hypothesize that among those with increased baseline symptom severity of negative affect (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 are 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; during the COVID-19 pandemic, the interventions are delivered virtually. Participants are 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 ≥15 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 are collected at baseline, at 3, 6, 9 and 12 months. Only baseline and 12 months post-entry data collection is conducted in person; the 3, 6, and 9-month data collection occurs online or by phone to minimize burden. Due the COVID-19 pandemic, the study protocol was modified to allow for the completion of all assessments and data collection virtually.

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.

\*The Results Reporting due date has been extended per PCORI to be 9/30/2023.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite Pain Severity
timeFrame: 6 months post-entry
measure: Composite Pain Severity
timeFrame: 12 months post-entry
measure: Physical Function
timeFrame: 6 months post-entry
measure: Physical Function
timeFrame: 12 months post-entry
measure: Average Pain Severity
timeFrame: 6 months post-entry
measure: Average Pain Severity
timeFrame: 12 months post-entry
Secondary outcomes:
measure: Health-Related Quality of Life (Physical Health)
timeFrame: 6 months post-entry
measure: Health-Related Quality of Life (Physical Health)
timeFrame: 12 months post-entry
measure: Health-Related Quality of Life (Mental Health)
timeFrame: 6 months post-entry
measure: Health-Related Quality of Life (Mental Health)
timeFrame: 12 months post-entry
measure: Average Daily Opioid Dose
timeFrame: 6 months post-entry
measure: Average Daily Opioid Dose
timeFrame: 12 months post-entry
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: Penn State University
name: Aleksandra E Zgierska, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Bruce P Barrett, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zgierska AE, Burzinski CA, Garland EL, Lennon RP, Jamison R, Nakamura Y, Barrett B, Sehgal N, Mirgain SA, Singles JM, Cowan P, Woods D, Edwards RR. Mindfulness-based therapy compared to cognitive behavioral therapy for opioid-treated chronic low back pain: Protocol for a pragmatic randomized controlled trial. Contemp Clin Trials. 2021 Nov;110:106548. doi: 10.1016/j.cct.2021.106548. Epub 2021 Sep 1.