The BEST Trial: Biomarkers for Evaluating Spine Treatments
NCT ID: NCT05396014
Last Updated: 2025-07-23
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
1014 participants
INTERVENTIONAL
2022-09-12
2024-10-22
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Implementation of the ACP Guideline for Low Back Pain (IMPACt-LBP)
NCT05626049
The Back Pain Consortium Research Program Study
NCT04870957
A Study of Duloxetine (LY248686) in Participants With Chronic Low Back Pain
NCT01855919
Pilot Study to Test the Effectiveness of Combining Conventional and Complementary Medicine to Treat Low Back Pain
NCT00118859
Mind-body Treatments for Chronic Back Pain
NCT03294148
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment Period 1: 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.
Enhanced Self-Care (ESC)
The Enhanced Self-Care intervention will be comprised of educational modules on evidence-based cognitive-behavioral self-management skills for pain. These modules will be provided digitally for self-administration over a period of 12 weeks. There will be no therapist associated with the delivery of these educational materials; however, after the first four modules, email or text messages will be used to make personalized recommendations for accessing additional modules based upon identified problems from the baseline assessment. Additionally, the walking program module will utilize Fitbit step tracking to allow participants to monitor their walking progress.
Treatment Period 1: 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.
Acceptance and Commitment Therapy (ACT)
ACT is a form of cognitive behavioral therapy that is well established for the treatment of chronic pain. The goal of ACT is to build psychological flexibility thereby interrupting pain avoidance behavior patterns. Participants randomized to ACT will take part in 12 sessions over the course of 12 weeks. Sessions will be delivered as a combination of 4 remote face-to-face visits with a therapist and 8 therapist-supported online sessions (self-directed online modules supported by provider coaching). Online sessions will focus on helping participants accept pain, connect with negative thoughts and emotions, develop mindfulness and identify and commit to values and goals that are important to them. During face-to-face sessions with the therapist, participants will be encouraged to share their experience of skills practice and mastery, provide examples of skill use at home, and describe what barriers they encountered.
Treatment Period 1: 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.
Evidence-Based Exercise and Manual Therapy (EBEM)
Licensed physical therapists (PTs) or Doctors of Chiropractic (DCs) will rely on evidence-based guidance to direct decision-making on the particular type of manual and exercise therapy that may be best suited to an individual study participant. Special attention will be paid to the clinician's choice of language in regard to the purpose and expected outcomes of manual therapy in order to avoid enhancing catastrophizing ideations or preference for passive interventions. A total of 10 sessions will be provided over an 8-week treatment period. Two sessions per week are provided in the first two weeks followed by weekly sessions over the next 6 weeks. Treatment sessions will last approximately 60 minutes each.
Treatment Period 1: Duloxetine
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.
Duloxetine
Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for use in Chronic Low-Back Pain, and, as such, is included as a recommended therapy in nearly all current treatment guidelines for low back pain. Study participants will be treated with duloxetine for 12 weeks during the active treatment phase. At the time of randomization, the approved drug pharmacy at each study site will dispense between 185 and 192 duloxetine 30 mg capsules and provide to participants. This will ensure enough capsules to maintain up to a 60 mg dosage through the 12-week intervention phase and to taper the dose in the 13th week if needed.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Enhanced Self-Care (ESC)
The Enhanced Self-Care intervention will be comprised of educational modules on evidence-based cognitive-behavioral self-management skills for pain. These modules will be provided digitally for self-administration over a period of 12 weeks. There will be no therapist associated with the delivery of these educational materials; however, after the first four modules, email or text messages will be used to make personalized recommendations for accessing additional modules based upon identified problems from the baseline assessment. Additionally, the walking program module will utilize Fitbit step tracking to allow participants to monitor their walking progress.
Acceptance and Commitment Therapy (ACT)
ACT is a form of cognitive behavioral therapy that is well established for the treatment of chronic pain. The goal of ACT is to build psychological flexibility thereby interrupting pain avoidance behavior patterns. Participants randomized to ACT will take part in 12 sessions over the course of 12 weeks. Sessions will be delivered as a combination of 4 remote face-to-face visits with a therapist and 8 therapist-supported online sessions (self-directed online modules supported by provider coaching). Online sessions will focus on helping participants accept pain, connect with negative thoughts and emotions, develop mindfulness and identify and commit to values and goals that are important to them. During face-to-face sessions with the therapist, participants will be encouraged to share their experience of skills practice and mastery, provide examples of skill use at home, and describe what barriers they encountered.
Evidence-Based Exercise and Manual Therapy (EBEM)
Licensed physical therapists (PTs) or Doctors of Chiropractic (DCs) will rely on evidence-based guidance to direct decision-making on the particular type of manual and exercise therapy that may be best suited to an individual study participant. Special attention will be paid to the clinician's choice of language in regard to the purpose and expected outcomes of manual therapy in order to avoid enhancing catastrophizing ideations or preference for passive interventions. A total of 10 sessions will be provided over an 8-week treatment period. Two sessions per week are provided in the first two weeks followed by weekly sessions over the next 6 weeks. Treatment sessions will last approximately 60 minutes each.
Duloxetine
Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for use in Chronic Low-Back Pain, and, as such, is included as a recommended therapy in nearly all current treatment guidelines for low back pain. Study participants will be treated with duloxetine for 12 weeks during the active treatment phase. At the time of randomization, the approved drug pharmacy at each study site will dispense between 185 and 192 duloxetine 30 mg capsules and provide to participants. This will ensure enough capsules to maintain up to a 60 mg dosage through the 12-week intervention phase and to taper the dose in the 13th week if needed.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIH
University of North Carolina, Chapel Hill
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Kevin Anstrom, PhD
Role: PRINCIPAL_INVESTIGATOR
UNC Chapel Hill
Matthew Mauck, PhD
Role: PRINCIPAL_INVESTIGATOR
UNC Chapel Hill
Gwendolyn Sowa, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
Daniel Clauw, MD
Role: PRINCIPAL_INVESTIGATOR
University of Michigan
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Stanford University
Redwood City, California, United States
University of California, San Diego
San Diego, California, United States
University of California, San Francisco
San Francisco, California, 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 Michigan
Ann Arbor, Michigan, 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
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
University of Washington
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Rowland B, Barth KS, Bell KM, Brooks AK, Chadwick AL, Cleven A, Hurley RW, Mackey S, Patel KV, Piva SR, Schneider MJ, Al-Kadhi F, Asante-Nketiah B, Bagaason S, Batorsky A, Borckardt JJ, Bowden AE, Carey TS, Castellanos J, Chen L, Chidgey B, Dalton D, Dufour JS, Eberting JL, Eller SM, Fields AJ, Fritz JM, Fu A, Ghulamhussain I, Goolsby RW, Greco CM, Grim S, Gunn CA, Hanes L, Harris RE, Harte SE, Hassett AL, Helton K, Hoffmeyer A, Ivanova A, Jones Berkeley S, Kaplan C, Kidwell KM, Knapik GG, Kosorok MR, Kurillo G, Li D, Lobo R, Long J, Lotz JC, Mageswaran P, Majumdar S, Mao J, Marras WS, McCracken LM, McCumber M, McLean SA, McMillan M, Mehling W, Mendoza R, Mitchell UH, Napadow V, O'Neill C, Pearson S, Peltier S, Rundell SD, Ryser S, Schrepf A, Schulze E, Sperger J, Vo N, Wallace MS, Wampler AM, Wasan AD, Weaver TE, Weber KA 2nd, Wilcox L, Williams DA, Wilson L, Woo JE, Zeidan F, Zhao B, Zhou B, Anstrom KJ, Clauw DJ, Sowa GA, Mauck MC. Baseline characteristics of participants in the Biomarkers for Evaluating Spine Treatments clinical trial: a sequential multiple assignment randomized trial for chronic low back paindagger. Pain Med. 2025 Aug 5:pnaf073. doi: 10.1093/pm/pnaf073. Online ahead of print.
Jones Berkeley S, Wedin S, Patidar SM, Margolies SO, Goetzinger AM, Mauck MC, Wasan AD, McCracken LM. Design and implementation of online acceptance and commitment therapy with enhanced therapist support for chronic low back pain (ACT for PAIN). Pain Med. 2025 Aug 1;26(8):451-458. doi: 10.1093/pm/pnaf026.
Mauck MC, Barth KS, Bell KM, Brooks AK, Chadwick AL, Gunn CA, Hurley RW, Ivanova A, Piva SR, Schneider MJ, Bailey JF, Bagaason S, Batorsky A, Borckardt JJ, Bowden AE, Carey TS, Castellanos J, Chen L, Chidgey B, Dalton D, Dufour JS, Fields AJ, Fritz JM, Goolsby RW, Greco CM, Harris RE, Harte S, Hassett AL, Hoffmeyer A, Jones Berkeley S, Kaplan C, Kidwell KM, Knapik GG, Kosorok MR, Kurillo G, Lobo R, Lotz JC, Mackey S, Mageswaran P, Majumdar S, Mao J, Marras WS, McCumber M, McLean SA, Mehling W, Mitchell UH, Napadow VJ, O'Neill C, Patel KV, Peltier S, Psioda M, Rowland B, Rundell SD, Schrepf A, Sperger J, Vo N, Wallace MS, Wasan AD, Weaver TE, Weber KA 2nd, Williams DA, Wilson L, Zeidan F, Zhao B, Anstrom KJ, Clauw DJ, Sowa GA. The design and rationale of the Biomarkers for Evaluating Spine Treatments trial: a sequential multiple assignment randomized trial. Pain Med. 2025 Sep 1;26(9):538-553. doi: 10.1093/pm/pnaf032.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
21-1972
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.