Chronic Low-back PainPhase 4BESTNCT05396014

The BEST Trial: Biomarkers for Evaluating Spine Treatments

A Phase 4 study testing Enhanced Self-Care (ESC), Acceptance and Commitment Therapy (ACT) and Evidence-Based Exercise and Manual Therapy (EBEM) in people with Chronic Low-back Pain, run by University of North Carolina, Chapel Hill at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Low-back Pain
What is being tested?: Enhanced Self-Care (ESC), Acceptance and Commitment Therapy (ACT) and Evidence-Based Exercise and Manual Therapy (EBEM)
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,014 participants
Where: 12 sitesUnited States
Study dates: 12 Sep 2022to 22 Oct 2024
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 16Show fewer

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)

Who cannot join

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

Show all 17Show fewer

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 locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

University of Michigan
Ann Arbor, Michigan, 48189
Massachusetts General Hospital/Brigham Women's Hospital, Harvard Medical School
Boston, Massachusetts, 02114
University of North Carolina Hospital Pain Management Clinic
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43203
University of Kansas Health System
Kansas City, Kansas, 66160
University of Pittsburgh
Pittsburgh, Pennsylvania, 15219
Stanford University
Redwood City, California, 94063
University of California, San Diego
San Diego, California, 92037
University of California, San Francisco
San Francisco, California, 94158
University of Washington
Seattle, Washington, 98104
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27517

Other trials in United States

About this study

The BEST Trial (Biomarkers for Evaluating Spine Treatments) is a National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)-sponsored clinical trial being conducted through the NIH Helping to End Addiction Long-term (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.

Read the 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.

Conditions: Chronic Low-back Pain
Being tested: Enhanced Self-Care (ESC), Acceptance and Commitment Therapy (ACT), Evidence-Based Exercise and Manual Therapy (EBEM), Duloxetine
Keywords: Pain, Back Pain
Medical subject headings: Pain, Back Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Enhanced Self-Care (ESC)Behavioural
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)Behavioural
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)Behavioural
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.
DuloxetineDrug
Also called Cymbalta
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.

Study groups in NCT05396014
Study group	Role	What they receive
Treatment Period 1: Enhanced Self-Care (ESC)	Active comparator	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. Receives: Behavioral: Enhanced Self-Care (ESC)
Treatment Period 1: Acceptance and Commitment Therapy (ACT)	Active comparator	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. Receives: Behavioral: Acceptance and Commitment Therapy (ACT)
Treatment Period 1: Evidence-Based Exercise and Manual Therapy (EBEM)	Active comparator	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. Receives: Behavioral: Evidence-Based Exercise and Manual Therapy (EBEM)
Treatment Period 1: Duloxetine	Active comparator	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. Receives: Drug: Duloxetine

What is being measured

The primary outcome is the main question the study is designed to answer.

Patient-Reported Pain Intensity and Interference Score
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.
Measured: Baseline, 24 Weeks

Secondary outcomes (7)

Patient-Reported Outcomes Measurement Information System-Pain Interference
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, and measures self-reported consequences of pain on relevant aspects of one's life. Results range from -34 to 34 (t-scores range from 41.6 to 75.6). For each t-score, 50 indicates the population mean with a standard deviation of 10. Lower scores indicate lower pain interference and a better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Measured: Baseline, 24 Weeks
Number of Participants Self-Reporting Taking Opioids
The number of participants self-reporting taking opioids ("Yes" response) is measured by a single question, "Are you currently taking any opioid pain medication on a daily basis?".
Measured: 24 Weeks
Patient-Reported Outcomes Measurement Information System- Physical Function
Physical function is measured by the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) Short Form 6b. The PROMIS-PF Short Form 6b is a series of 6 questions. T-scores range from 21.6 to 58.7 and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -37.1 to 37.1, with higher physical function scores indicating a better outcome and increased physical functioning at 24 Weeks compared to Baseline. A higher physical function is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Measured: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Score
Depression score is measured by the Patient-Reported Outcomes Measurement Information System (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. T-scores range from 41.0 to 79.4), and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -38.4 to 38.4, with higher scores indicating increased depression at 24 Weeks compared to Baseline. A lower depression score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Measured: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety
Anxiety score is measured by the Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety (PROMIS-EDA) scale 4a. The PROMIS-EDA 4a is a series of 4 questions. T-scores range from 40.3 to 81.6, and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -41.3 to 41.3, with higher scores indicating increased anxiety at 24 Weeks compared to Baseline. A lower anxiety score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Measured: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System - Sleep Disturbance
Sleep disturbance is measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) short form 6a. The PROMIS short form 6a is a series of 6 questions. T-scores range from 31.7 to 76.1 and for each t-score, 50 indicates the population mean with a standard deviation of 10). Results range from -44.4 to 44.4, with higher scores indicating increased sleep disturbance at 24 Weeks compared to Baseline. A lower sleep disturbance score is the better outcome. PPROMIS measures are not used for clinical decision making but to describe participant symptoms.
Measured: Baseline, 24 Weeks
Sleep Duration
Sleep duration is measured by the Back Pain Consortium (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.
Measured: Baseline, 24 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Sep 202222 Oct 2024

First posted27 May 2022
Study start12 Sep 2022
Primary completion30 Jul 2024
Study completion22 Oct 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Chronic Low-back PainStudies of the same condition, open and under way.
More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: Sequential Multiple Assignment Randomized Trial (SMART)
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 1,014 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05396014
Sponsor's protocol ID: 21-1972
Other IDs: 1U24AR076730
Acronym: BEST
Status last verified: Aug 2024
First submitted: 24 May 2022
Last updated: 23 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: All relevant study data will be shared through NIH portals as required.

Publications

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 Nov 1;26(11):758-772. doi: 10.1093/pm/pnaf073.
PubMed 40794568
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.
PubMed 40249098
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.
PubMed 40205455

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Chronic Low-back Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The BEST Trial: Biomarkers for Evaluating Spine Treatments
ClinicalTrials.gov ID: NCT05396014
Acronym / sponsor ID: BEST / 21-1972
Conditions: Chronic Low-back Pain
Keywords: Pain, Back Pain
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,014 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study start: 12 Sep 2022 (actual)
Primary completion: 30 Jul 2024 (actual)
Study completion: 22 Oct 2024 (actual)
First posted: 27 May 2022 (actual)
Results: Posted 23 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Single blind (outcomes assessor)
Number of arms: 4
Model description: Sequential Multiple Assignment Randomized Trial (SMART)

Arm	Type	Receives
Treatment Period 1: Enhanced Self-Care (ESC)	Active comparator	Behavioral: 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)	Active comparator	Behavioral: 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)	Active comparator	Behavioral: 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: Duloxetine	Active comparator	Drug: DuloxetineThis 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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

Key exclusion criteria (17 listed)

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:
Any condition that, in the opinion of the investigator, would preclude the patient from being able to safely participate in in the trial

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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.	Behavioural	Treatment Period 1: Enhanced Self-Care (ESC)
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.	Behavioural	Treatment Period 1: Acceptance and Commitment Therapy (ACT)
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.	Behavioural	Treatment Period 1: Evidence-Based Exercise and Manual Therapy (EBEM)
DuloxetineAlso: CymbaltaDuloxetine 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.	Drug	Treatment Period 1: Duloxetine

Primary outcome

Patient-Reported Pain Intensity and Interference Score
Time frame: Baseline, 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.

7 secondary outcomes

Patient-Reported Outcomes Measurement Information System-Pain Interference
Time frame: Baseline, 24 Weeks
Number of Participants Self-Reporting Taking Opioids
Time frame: 24 Weeks
Patient-Reported Outcomes Measurement Information System- Physical Function
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Score
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety
Time frame: Baseline, 24 Weeks
Patient-Reported Outcomes Measurement Information System - Sleep Disturbance
Time frame: Baseline, 24 Weeks
Sleep Duration
Time frame: Baseline, 24 Weeks

Results and safety

Results posted to the registry on 23 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Acceptance and Commitment Therapy (ACT) Alone	63	28
ACT Plus Duloxetine, Moderate Treatment Response	8	8
ACT Plus Evidence Based Exercise and Manual Therapy (EBEM), Moderate Period 1 Treatment Response	8	8
ACT Plus Enhanced Self-Care Therapy (ESC), Moderate Period 1 Treatment Response	5	5
ACT Plus Duloxetine, Low Period 1 Treatment Response	12	12
ACT Plus Evidence Based Exercise and Manual Therapy (EBEM), Low Period 1 Treatment Response	21	21
ACT Plus Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	20	20
ACT Followed by Duloxetine, Low Period 1 Treatment Response	12	12
ACT Followed by Evidence Based Exercise and Manual Therapy (EBEM), Low Period 1 Treatment Response	22	22
ACT Followed by Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	28	28
ACT Followed by Duloxetine, Poor Period 1 Treatment Response	2	2
ACT Followed by Evidence Based Exercise and Manual Therapy (EBEM), Poor Period 1 Treatment Response	1	1
ACT Followed by Enhanced Self-Care Therapy (ESC), Poor Period 1 Treatment Response	1	1
Duloxetine Alone	71	48
Duloxetine Plus Acceptance and Commitment Therapy (ACT), Moderate Period 1 Treatment Response	9	9
Duloxetine Plus Evidence Based Exercise & Manual Therapy(EBEM), Moderate Period 1 Treatment Response	4	4
Duloxetine Plus Enhanced Self-Care Therapy (ESC), Moderate Period 1 Treatment Response	4	4
Duloxetine Plus Acceptance and Commitment Therapy (ACT), Low Period 1 Treatment Response	4	4
Duloxetine Plus Evidence Based Exercise and Manual Therapy (EBEM), Low Period 1 Treatment Response	8	8
Duloxetine Plus Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	9	9
Duloxetine Followed by Acceptance and Commitment Therapy (ACT), Low Period 1 Treatment Response	25	25
Duloxetine Followed by Evidence Based Exercise and Manual Therapy(EBEM), Low Period 1 Trt Response	26	26
Duloxetine Followed by Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	26	26
Duloxetine Followed by Acceptance and Commitment Therapy (ACT), Poor Period 1 Treatment Response	4	4
Duloxetine Followed by Evidence Based Exercise and Manual Therapy (EBEM), Poor Period 1 Trt Response	3	3
Duloxetine Followed by Enhanced Self-Care Therapy (ESC), Poor Period 1 Treatment Response	5	5
Evidence Based Exercise and Manual Therapy (EBEM) Alone	97	71
EBEM Plus Duloxetine, Moderate Period 1 Treatment Response	5	5
EBEM Plus Acceptance and Commitment Therapy (ACT), Moderate Period 1 Treatment Response	15	15
EBEM Plus Enhanced Self-Care Therapy (ESC), Moderate Period 1 Treatment Response	12	12
EBEM Plus Duloxetine, Low Period 1 Treatment Response	6	6
EBEM Plus Acceptance and Commitment Therapy (ACT), Low Period 1 Treatment Response	9	9
EBEM Plus Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	14	14
EBEM Followed by Duloxetine, Low Period 1 Treatment Response	13	13
EBEM Followed by Acceptance and Commitment Therapy (ACT), Low Period 1 Treatment Response	12	12
EBEM Followed by Enhanced Self-Care Therapy (ESC), Low Period 1 Treatment Response	7	7
EBEM Followed by Duloxetine, Poor Period 1 Treatment Response	4	4
EBEM Followed by Acceptance and Commitment Therapy (ACT), Poor Period 1 Treatment Response	1	1
EBEM Followed by Enhanced Self-Care Therapy (ESC), Poor Period 1 Treatment Response	4	4
Enhanced Self-Care Therapy (ESC) Alone	46	16
ESC Plus Duloxetine, Moderate to Low Period 1 Treatment Response	41	41
ESC Plus Acceptance and Commitment Therapy (ACT), Moderate to Low Period 1 Treatment Response	59	59
ESC Plus Evidence Based Exercise and Manual Therapy (EBEM), Moderate to Low Period 1 Trt Response	59	59

Primary outcome: Patient-Reported Pain Intensity and Interference Score

Time frame: Baseline, 24 Weeks. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Stage 1: Acceptance and Commitment Therapy (ACT) n = 203	Stage 1: Duloxetine n = 198	Stage 1: Evidence Based Exercise and Manual Therapy (EBEM) n = 199	Stage 1: Enhanced Self-Care Therapy (ESC) n = 205
Value	4.16 (3.74 to 4.58)	3.86 (3.43 to 4.28)	3.57 (3.15 to 3.99)	4.72 (4.3 to 5.14)

Population analysed: The analysis population is the all-randomized population to Stage 1 interventions.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events were recorded between the time the participant provided informed consent at Week -2 (Run-in Period: Weeks -2 to 0) through 4 weeks after their last treatment (Stage 1 intervention period: Weeks 0 to 12; Stage 2 intervention period: Weeks 12 to 24), up to 30 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stage 1: Acceptance and Commitment Therapy (ACT)	4 of 191 (2.1%)	2 of 191 (1%)	0 of 191
Stage 1: Duloxetine	1 of 172 (0.6%)	92 of 172 (53.5%)	0 of 172
Stage 1: Evidence Based Exercise and Manual Therapy (EBEM)	6 of 184 (3.3%)	7 of 184 (3.8%)	0 of 184
Stage 1: Enhanced Self-Care Therapy (ESC)	2 of 205 (1%)	4 of 205 (2%)	0 of 205
Stage 2: Acceptance and Commitment Therapy (ACT)	4 of 65 (6.2%)	1 of 65 (1.5%)	0 of 65
Stage 2: Duloxetine	0 of 71 (0%)	29 of 71 (40.8%)	0 of 71
Stage 2: Evidence Based Exercise and Manual Therapy (EBEM)	3 of 110 (2.7%)	3 of 110 (2.7%)	0 of 110
Stage 2: Enhanced Self-Care Therapy (ESC)	2 of 85 (2.4%)	0 of 85 (0%)	0 of 85
Stage 2: ACT and Duloxetine	1 of 33 (3%)	12 of 33 (36.4%)	0 of 33
Stage 2: ACT and EBEM	0 of 52 (0%)	3 of 52 (5.8%)	0 of 52
Stage 2: ACT and ESC	4 of 84 (4.8%)	2 of 84 (2.4%)	0 of 84
Stage 2: Duloxetine and EBEM	0 of 22 (0%)	4 of 22 (18.2%)	0 of 22
Stage 2: Duloxetine and ESC	1 of 54 (1.9%)	18 of 54 (33.3%)	0 of 54
Stage 2: EBEM and ESC	4 of 85 (4.7%)	5 of 85 (5.9%)	0 of 85

Limitations and caveats (from the sponsor): The BEST Trial is a sequential, multiple-assignment randomized trial designed to estimate the optimal treatment (or sequence) for chronic low back pain based on unique biomarkers and response to treatment. As this precision-medicine focus dictates individualized rather than arm-level contrasts, no between-arm comparative-effectiveness analyses are planned as primary analyses. The primary goal of this study was to identify predictive biomarkers for each treatment not comparative effectiveness.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40794568Rowland 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 Nov 1;26(11):758-772. doi: 10.1093/pm/pnaf073.
Derived from this study: PubMed 40249098Jones 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.
Derived from this study: PubMed 40205455Mauck 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.
Individual participant dataSharing planned: Yes. All relevant study data will be shared through NIH portals as required.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kevin Anstrom, PhD principal investigator

UNC Chapel Hill

Matthew Mauck, PhD principal investigator

UNC Chapel Hill

Gwendolyn Sowa, PhD principal investigator

University of Pittsburgh

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patient-Reported Pain Intensity and Interference Score (time frame: Baseline, 24 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05396014, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.