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The BEST Trial: Biomarkers for Evaluating Spine Treatments

Phase 4
Completed
Conditions
Chronic Low-back Pain
Interventions
Behavioral: Enhanced Self-Care (ESC)
Behavioral: Acceptance and Commitment Therapy (ACT)
Behavioral: Evidence-Based Exercise and Manual Therapy (EBEM)
Registration Number
NCT05396014
Lead Sponsor
University of North Carolina, Chapel Hill
Brief Summary

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 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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1014
Inclusion Criteria

To be eligible, an individual must meet all of the following inclusion criteria:

  • Ability to read and understand English

  • Provision of signed and dated informed consent form(s)

  • Willing and able to receive study-related messages and survey links via email

  • Willing and able to receive study-related phone calls

  • Age 18 years old or older

  • Low-back pain for at least 3 months and occurring on at least half the days in the past 6 months

  • Contraindicated to no more than one of the study interventions at the time of eligibility assessment(s)

  • Eligible to receive at least three of the four study interventions and willing to receive any intervention for which they are eligible

  • A PEG score 4 or higher prior to the Run-in period

  • Willing and able to undergo required phenotyping

  • Regular reliable access to an internet-enabled device such as a smart phone, tablet, or laptop computer

  • Meet Run-in period engagement eligibility criteria:

    o Completion of two Run-in study information modules prior to period 1 randomization (Visit 0)

  • Low-back pain more severe than pain in other parts of the body

  • Available to complete the full study protocol (approximately 9 months)

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

  • Pregnant at the time of Visit 0 (Baseline)

  • Affirmative participant response to any of the following conditions:

    • Progressive neurodegenerative disease
    • History of discitis osteomyelitis (spine infection) or spine tumor
    • History of ankylosing spondylitis, rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis, or lupus
    • History of cauda equina syndrome or spinal radiculopathy with functional motor deficit (strength <4/5 on manual motor testing)
    • Diagnosis of any vertebral fracture in the last 6 months
    • Osteoporosis requiring pharmacologic treatment other than vitamin D, calcium supplements, or bisphosphonates.
    • History of any bone-related cancer or cancer that metastasized to the bone
    • Currently in treatment for any non-skin cancer or plan to start non-skin cancer treatment in the next 12 months
    • History of any non-skin cancer treatment in the last 24 months
    • Visual or hearing difficulties that would preclude participation
    • Uncontrolled drug/alcohol addiction
    • Individuals actively pursuing disability or workers compensation or involved in active personal injury-related litigation
    • Currently participating in another interventional pain study
  • Any condition that, in the opinion of the investigator, would preclude the patient from being able to safely participate in in the trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Treatment Period 1: Enhanced Self-Care (ESC)Enhanced Self-Care (ESC)This arm includes participants who are randomized to ESC in Treatment Period 1. Depending on their response to Treatment 1 measured at 12 Weeks post-initial randomization, participants in this arm will stay on ESC or be randomized to augment ESC with an additional treatment during Treatment Period 2.
Treatment Period 1: Acceptance and Commitment Therapy (ACT)Acceptance and Commitment Therapy (ACT)This arm includes participants who are randomized to ACT in Treatment Period 1. Depending on their response to Treatment 1 measured at 12 Weeks post-initial randomization, participants in this arm will stay on ACT, augment ACT with an additional treatment, or switch to a new treatment during Treatment Period 2.
Treatment Period 1: Evidence-Based Exercise and Manual Therapy (EBEM)Evidence-Based Exercise and Manual Therapy (EBEM)This arm includes participants who are randomized to EBEM in Treatment Period 1. Depending on their response to Treatment 1 measured at 12 Weeks post-initial randomization, participants in this arm will stay on EBEM, augment EBEM with an additional treatment, or switch to a new treatment during Treatment Period 2.
Treatment Period 1: DuloxetineDuloxetineThis arm includes participants who are randomized to Duloxetine in Treatment Period 1. Depending on their response to Treatment 1 measured at 12 Weeks post-initial randomization, participants in this arm will stay on Duloxetine, augment Duloxetine with an additional treatment, or switch to a new treatment during Treatment Period 2.
Primary Outcome Measures
NameTimeMethod
Patient-Reported Pain Intensity and Interference ScoreBaseline, 24 Weeks

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.

Secondary Outcome Measures
NameTimeMethod
Pain InterferenceBaseline, 24 Weeks

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. Results range from -34 to 34 (t-scores range from 41.6 to 75.6), with higher scores indicating increased pain interference at 24 Weeks compared to Baseline.

Incidence of Any Opioid UseBaseline, 24 Weeks

Incidence of opioid use is measured by a single question, "Are you currently taking any opioid pain medication on a daily basis?" Participants respond with "Yes", "No", or "Not Sure".

Physical FunctionBaseline, 24 Weeks

Physical function is measured by the PROMIS-PF Short Form 6b. The PROMIS-PF Short Form 6b is a series of 6 questions. Results range from -37.1 to 37.1 (t-scores range from 21.6 to 58.7), with higher scores indicating increased physical functioning at 24 Weeks compared to Baseline.

Depression ScoreBaseline, 24 Weeks

Depression score is measured by the 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. Results range from -38.4 to 38.4 (t-scores range from 41.0 to 79.4), with higher scores indicating increased depression at 24 Weeks compared to Baseline.

Anxiety ScoreBaseline, 24 Weeks

Anxiety score is measured by the PROMIS Emotional Distress-Anxiety scale (PROMIS-EDA 4a). The PROMIS-EDA 4a is a series of 4 questions. Results range from -41.3 to 41.3 (t-scores range from 40.3 to 81.6), with higher scores indicating increased anxiety at 24 Weeks compared to Baseline.

Sleep DisturbanceBaseline, 24 Weeks

Sleep disturbance is measured by the PROMIS short form 6a. The PROMIS short form 6a is a series of 6 questions. Results range from -44.4 to 44.4 (t-scores range from 31.7 to 76.1), with higher scores indicating increased sleep disturbance at 24 Weeks compared to Baseline.

Sleep DurationBaseline, 24 Weeks

Sleep duration is measured by the 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.

Trial Locations

Locations (12)

Stanford University

🇺🇸

Redwood City, California, United States

University of Washington

🇺🇸

Seattle, Washington, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

University of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, 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 California, San Diego

🇺🇸

San Diego, California, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

The Ohio State University Wexner Medical Center

🇺🇸

Columbus, Ohio, 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

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

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