The BEST Trial: Biomarkers for Evaluating Spine Treatments

University of North Carolina (UNC)

Status and phase: Active, not recruiting; Phase 4

Conditions: Chronic Low-back Pain

Treatments: Behavioral: Enhanced Self-Care (ESC); Behavioral: Evidence-Based Exercise and Manual Therapy (EBEM); Behavioral: Acceptance and Commitment Therapy (ACT); Drug: Duloxetine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05396014

1U24AR076730 (U.S. NIH Grant/Contract)

21-1972

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,014 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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1,014 participants in 4 patient groups

Treatment Period 1: Enhanced Self-Care (ESC)

Active Comparator group

Description:

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:

Behavioral: Enhanced Self-Care (ESC)

Treatment Period 1: Acceptance and Commitment Therapy (ACT)

Active Comparator group

Description:

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:

Behavioral: Acceptance and Commitment Therapy (ACT)

Treatment Period 1: Evidence-Based Exercise and Manual Therapy (EBEM)

Active Comparator group

Description:

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:

Behavioral: Evidence-Based Exercise and Manual Therapy (EBEM)

Treatment Period 1: Duloxetine

Active Comparator group

Description:

This 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.

Treatment:

Drug: Duloxetine