Clinical trial NCT05396014: The BEST Trial: Biomarkers for Evaluating Spine Treatments
Official title: The BEST Trial: Biomarkers for Evaluating Spine Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Low-back Pain
Keywords: Pain
Back Pain
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2022-05-27
Enrollment: 1014
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential Multiple Assignment Randomized Trial (SMART)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient-Reported Pain Intensity and Interference Score
timeFrame: Baseline, 24 Weeks
Secondary outcomes:
measure: Pain Interference
timeFrame: Baseline, 24 Weeks
measure: Incidence of Any Opioid Use
timeFrame: Baseline, 24 Weeks
measure: Physical Function
timeFrame: Baseline, 24 Weeks
measure: Depression Score
timeFrame: Baseline, 24 Weeks
measure: Anxiety Score
timeFrame: Baseline, 24 Weeks
measure: Sleep Disturbance
timeFrame: Baseline, 24 Weeks
measure: Sleep Duration
timeFrame: Baseline, 24 Weeks
Other outcomes:
Locations:
city: Redwood City
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Kansas City
country: United States
facility: University of Kansas Health System
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital/Brigham Women's Hospital, Harvard Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital Pain Management Clinic
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: UNC Chapel Hill
name: Kevin Anstrom, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC Chapel Hill
name: Matthew Mauck, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Gwendolyn Sowa, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Daniel Clauw, MD
role: PRINCIPAL_INVESTIGATOR
References: