Chronic Low-back Pain
Conditions
Keywords
Pain, Back Pain
Brief summary
This study is being completed to better understand who benefits from different chronic pain treatments and how these treatments work. This study will include a four week run-in period for all cLBP participants. After completing the PainGuide (online or smart phone accessible website) run-in period, participants will be assessed using either the light or light plus deep phenotyping assessment battery and those who minimal or modest improvement in their pain (based on PGIC) will be randomized to one of four 8-week treatments (mindfulness-based stress reduction (MBSR), physical therapy (PT) and exercise, acupressure self-management, or duloxetine). In addition, participants will complete study visits including physical exams, complete surveys, provide samples (blood,saliva, etc.), wear an electronic wrist device at certain times, and have Magnetic resonance imaging (MRIs) during the study. Following one of the 4 treatments (8 weeks) if participants have a certain level of pain (that meets eligibility for more treatment) they will be then randomized to complete one of the 3 treatments that was not already assigned to them. The study hypothesizes the following: that this interventional response phenotyping can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based interventions for chronic lower back pain (cLBP).
Detailed description
In addition, the following mechanistic hypothesis and Aims are included: Mindfulness-Based Stress Reduction: Aim 2: the study predicts that patients with chronic low back pain (cLBP) will preferentially respond to this therapy if PROs indicate higher levels of pain catastrophizing, as measured by the Pain Catastrophizing Scale, or lower scores on the Experiences Questionnaire. Aim 3: the study hypothesizes that cLBP patients with decreased activation in response to pain in the subgenual anterior cingulate cortex (sgACC) and Prefrontal Cortex and increased activation in somatosensory cortex (S1) and thalamus will respond preferentially to MBSR. Physical Therapy (PT) and Exercise Aim 2: The primary hypothesis for the light phenotyping protocol is those individuals with the highest scores on the Fear Avoidance Beliefs Questionnaire and lowest scores for PROMIS Self-Efficacy for Managing Symptoms will be most likely to improve from PT/Exercise program. Aim 3: the study hypothesis that low vagal tone and high basal inflammation will predict responsiveness to the PT/Exercise program. Acupressure: Aim 2: The study hypothesizes that females with cLBP will respond better to acupressure than men, as will those with higher scores on the 2011 Fibromyalgia Survey Questionnaire. Aim 3: The study predicts that cLBP patients with higher posterior insula glutamate and/or greater insula - Default Mode Network (DMN) connectivity (as well as increased DMN-S1 connectivity Duloxetine: Aim 2: the study hypothesizes that it will replicate previous studies suggesting that participants with cLBP will preferentially respond to this therapy if patient reported outcomes indicate stronger elements of either neuropathic pain (indicated by a high PainDETECT score) or centralized/nociplastic pain (indicated by more widespread pain on the 2011 Fibromyalgia Survey Questionnaire). Aim 3: the study anticipates then that deficient pain inhibition on quantitative sensory testing, decreased periaqueductal gray (PAG)-insula connectivity, and elevated stimulated inflammatory responses will be associated with a positive response to centrally-acting duloxetine. Additionally, a subset of individuals (n=160) from these groups will be asked to participate in an expanded phenotyping study that will include structural and functional brain neuroimaging, quantitative sensory testing (QST), plasma measures of inflammation, and digital measurement of autonomic tone.
Interventions
BEHAVIORALPainGuide
A 4-week, online, self-management program for pain known as PainGuide (online or smart phone). Participants will use this during the run-in period as well as after the run-in period.
BEHAVIORALMBSR
In this group (mindfulness-based stress reduction) participants will take part in 9 group sessions. The groups sessions will be divided into 8 weekly 2-hour groups sessions and one 6-hour retreat. During the sessions participants will practice mindfulness exercises directed by the a MBSR therapist. Additionally, participants will also be asked to practice daily formal mindfulness at home using audio recordings of 30-45 minute guided meditation exercises. These audio recordings can be accessed online. The sessions may take place in-person or virtually.
BEHAVIORALPT and exercise
Participants will take part in 10 physical therapy visits over the course of 8 weeks. Participants will meet with the physical therapist twice a week for a 1-hour session for weeks 1 and 2 and then weekly for the remaining 6 weeks. The physical therapist will tailor a program to the participant's needs according to recommended PT practice guidelines that will include in-person treatment, home exercise prescription, and encouragement of progressive, low-intensity, submaximal fitness and endurance activities, such as walking. Participants will be given a home program of exercises to be done daily and asked to engage in daily walking with a set goal based on the individual's capacity and current fitness level. Walking was selected as the aerobic exercise of focus for this treatment because it is recommended for patients with all levels of pain severity, is highly feasible to complete, and has shown effects on outcomes such as pain and disability.
DEVICESelf -administered acupressure
A device called the AcuWand will be used to administer the self-acupressure intervention for approximately 30 minutes daily for 8 weeks. Participants will use a mobile application (app) called MeTime that will have daily instructions on how to use the AcuWand. Research staff will show participants how to use the AcuWand and MeTime app. In addition, participants will keep a daily log to track at-home acupressure sessions.
DRUGDuloxetine
For days 1-7, patients will take 30mg of duloxetine once a day, in the morning. Starting day 8, participants tolerating the medication will be escalated to 60mg once a day. They will also have the option of staying at 30mg, once a day or stopping the medication. At the end of the 8-week intervention period, participants will have the option to continue the medication commercially (non-study medication) under the care of their physician or taper off the medication. During the entire 8-week intervention, patients will be asked to keep a daily log of medication dosage, any missed doses, and any side-effects they may have experienced.
DEVICEPro-Diary monitor
Participants will wear during 5 separate 7-day home monitoring periods to assess physical activity (objectively measured via accelerometry), and ecological momentary assessment (EMA) of mental and physical symptoms. EMA will be collected during Weeks 1, 6, 15, 24 and 36.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Sequential, multiple assignment, randomized trial (SMART) design
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
for Light Phenotyping (all participants): * Definition of cLBP described in the NIH Task Force Report on Research Standards for Chronic Low Back Pain (for example (i.e.), low back pain present at least six months, and present more than half of those days. * Individuals must have the eligible protocol pain interference score on PROMIS Pain Interference. * Individuals must be willing to be randomized to receive any of the four proposed treatments.
Exclusion criteria
for Light Phenotyping (all participants): * History of discitis osteomyelitis (spine infection) or spine tumor * History of ankylosing spondylitis, rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis, 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 treatment other than vitamin D and calcium supplements * Cancer (History of any bone-related cancer or cancer that metastasized to the bone, Currently in treatment for any cancer or plan to start cancer treatment in the next 12 months, History of any cancer treatment in the last 24 months) * Life expectancy less than 2 years * Unable to speak and write English * Visual or hearing difficulties that would preclude participation * Presence of any history that would preclude scanning in magnetic resonance imaging (MRI) * Uncontrolled drug/alcohol addiction * Individuals receiving disability or compensation within the past year, or involved in litigation * Pregnancy or breastfeeding * History of allergy to duloxetine * Individuals on high doses of opioids (over 100 oral morphine equivalents (OME) per day) * Scheduled back surgery, back surgery within the last year, or more than one back surgery in the past. * Expecting to receive an injection of surgical procedure within the next year for their cLBP * Current/planned (in the next 2 years) enrollment in another study of a device or investigational drug that would interfere with this study, this may include participation in a blinded trial. * Any other diseases or conditions that would make a patient unsuitable for study participation as determined by the site principal investigators. This would include but not be limited to severe psychiatric disorders, active suicidal ideations or history of suicide attempts, and an uncontrolled drug and/or alcohol addiction Contraindications to Study Intervention: duloxetine * certain medications (per protocol) * renal dysfunction (creatinine clearance \<30 milliliters per minute (mL/min) or End- Stage Renal Failure) * Hepatic dysfunction: Liver function tests (LFTs) elevated times 1.5 Contraindications to Study Intervention: Acupressure * Currently receiving acupressure or acupuncture through formal therapy Contraindications to Study Intervention: MBSR * Current participation in a structured MBSR program Contraindications to Study Intervention: PT & Exercise * Currently receiving any type of structured manual therapy or exercise treatment for low-back pain. * Contraindication for manual therapy and/or participation in an exercise program Inclusion Criteria for Deep Phenotyping (subset 160 participants): * Right hand dominant (such as the hand used when writing or throwing/catching a ball) * Normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing * No contraindications to MRI (i.e., metal implants) * Willingness to refrain from taking any as needed medications, including pain medications such as Nonsteroidal anti-inflammatory drugs (i.e., Motrin, Advil, Aleve), acetaminophen, and opioids, for 8 hours before undergoing neuroimaging and 10.1 Quantitative Sensory Testing (QST) * Willingness to refrain from alcohol and nicotine on the day of QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed) * Willingness to refrain from any unusual physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable) * Able to lie still on back for 2 hours during MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3) | week 6 (T2), week 15 (T3) | The PROMIS pain interference consists of 4 questions on a Likert scale ranging from 'Not at all (1) to Very much (5). Total scores are between 4 and 20, with higher scores indicating increased pain interference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3) | week 6 (T2), week 15 (T3) | This is a 3 question scale where participants select a between 0 (no pain) to 10 (pain is bad and completely interferes). Higher the scores the worse the pain. |
| Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | week 15 (T3) | This is a 1 question item where participants described their perceived improvement between T2 and T3 by selecting a score between 1 and 7, where 1 indicated very much improved and 7 indicated very much worse. The lower the score, the greater improvement in perceived pain. Data is presented as count of participants who scored their improvement as a 1 or a 2 and those who scored their improvement as 3 or higher. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from June 1, 2021-June 27, 2024, through Michigan Medicine clinics (Back & Pain Center, Physical Medicine, Family Medicine, Neurosurgery) and community/online sources (UMHealthResearch.org, Facebook, MLive, flyers, radio). Of 6,965 screened, 494 eligible participants completed a baseline visit.
Pre-assignment details
Participants completed a 4-week online PainGuide run-in before randomization. At T2, those with PGIC ≥ 2 were randomized to one of four 8-week treatments (MBSR, PT/exercise, acupressure, or duloxetine). Participants with PGIC \< 2 entered follow-up only and were not randomized. Screen failures were those who did not meet eligibility criteria were withdrawn from the study.
Participants by arm
| Arm | Count |
|---|---|
| Acupressure Self -administered acupressure: A device called the AcuWand will be used to administer the self-acupressure intervention for approximately 30 minutes daily for 8 weeks. Participants will use a mobile application (app) called MeTime that will have daily instructions on how to use the AcuWand. Research staff will show participants how to use the AcuWand and MeTime app. In addition, participants will keep a daily log to track at-home acupressure sessions.
Pro-Diary monitor: Participants will wear during 5 separate 7-day home monitoring periods to assess physical activity (objectively measured via accelerometry), and ecological momentary assessment (EMA) of mental and physical symptoms. EMA will be collected during Weeks 1, 6, 15, 24 and 36. | 101 |
| PT and Exercise PT and exercise: Participants will take part in 10 physical therapy visits over the course of 8 weeks. Participants will meet with the physical therapist twice a week for a 1-hour session for weeks 1 and 2 and then weekly for the remaining 6 weeks. The physical therapist will tailor a program to the participant's needs according to recommended PT practice guidelines that will include in-person treatment, home exercise prescription, and encouragement of progressive, low-intensity, submaximal fitness and endurance activities, such as walking.
Participants will be given a home program of exercises to be done daily and asked to engage in daily walking with a set goal based on the individual's capacity and current fitness level. Walking was selected as the aerobic exercise of focus for this treatment because it is recommended for patients with all levels of pain severity, is highly feasible to complete, and has shown effects on outcomes such as pain and disability.
Pro-Diary monitor: Participants will wear during 5 separate 7-day home monitoring periods to assess physical activity (objectively measured via accelerometry), and ecological momentary assessment (EMA) of mental and physical symptoms. EMA will be collected during Weeks 1, 6, 15, 24 and 36. | 102 |
| MBSR (Mindfulness-based Stress Reduction) MBSR: In this group (mindfulness-based stress reduction) participants will take part in 9 group sessions.
The groups sessions will be divided into 8 weekly 2-hour groups sessions and one 6-hour retreat. During the sessions participants will practice mindfulness exercises directed by the a MBSR therapist. Additionally, participants will also be asked to practice daily formal mindfulness at home using audio recordings of 30-45 minute guided meditation exercises. These audio recordings can be accessed online. The sessions may take place in-person or virtually.
Pro-Diary monitor: Participants will wear during 5 separate 7-day home monitoring periods to assess physical activity (objectively measured via accelerometry), and ecological momentary assessment (EMA) of mental and physical symptoms. EMA will be collected during Weeks 1, 6, 15, 24 and 36. | 101 |
| Duloxetine Duloxetine: For days 1-7, patients will take 30mg of duloxetine once a day, in the morning. Starting day 8, participants tolerating the medication will be escalated to 60mg once a day. They will also have the option of staying at 30mg, once a day or stopping the medication. At the end of the 8-week intervention period, participants will have the option to continue the medication commercially (non-study medication) under the care of their physician or taper off the medication. During the entire 8-week intervention, patients will be asked to keep a daily log of medication dosage, any missed doses, and any side-effects they may have experienced.
Pro-Diary monitor: Participants will wear during 5 separate 7-day home monitoring periods to assess physical activity (objectively measured via accelerometry), and ecological momentary assessment (EMA) of mental and physical symptoms. EMA will be collected during Weeks 1, 6, 15, 24 and 36. | 96 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| T1 - Pre-Randomization: PainGuide run-in | Lost to Follow-up | 0 | 0 | 0 | 0 | 37 | 0 |
| T1 - Pre-Randomization: PainGuide run-in | Physician Decision | 0 | 0 | 0 | 0 | 3 | 0 |
| T1 - Pre-Randomization: PainGuide run-in | Screen Failure | 0 | 0 | 0 | 0 | 2 | 0 |
| T1 - Pre-Randomization: PainGuide run-in | Withdrawal by Subject | 0 | 0 | 0 | 0 | 35 | 0 |
| T2 (Randomization) - T3 | Adverse Event | 1 | 1 | 0 | 0 | 0 | 0 |
| T2 (Randomization) - T3 | Lost to Follow-up | 7 | 0 | 7 | 3 | 0 | 0 |
| T2 (Randomization) - T3 | Missed Timepoint | 4 | 3 | 3 | 2 | 0 | 12 |
| T2 (Randomization) - T3 | Physician Decision | 0 | 0 | 2 | 1 | 0 | 0 |
| T2 (Randomization) - T3 | Withdrawal by Subject | 11 | 8 | 11 | 7 | 0 | 1 |
| T3 (Re-randomization) - T4 | Adverse Event | 0 | 1 | 0 | 1 | 0 | 0 |
| T3 (Re-randomization) - T4 | Lost to Follow-up | 8 | 6 | 7 | 6 | 0 | 2 |
| T3 (Re-randomization) - T4 | Missed Timepoint | 3 | 1 | 2 | 2 | 0 | 23 |
| T3 (Re-randomization) - T4 | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 |
| T3 (Re-randomization) - T4 | Withdrawal by Subject | 11 | 5 | 10 | 3 | 0 | 1 |
| T4 - T5 (Follow-Up) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 21 |
| T4 - T5 (Follow-Up) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 2 |
| T4 - T5 (Follow-Up) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 7 |
Baseline characteristics
| Characteristic | PT and Exercise | MBSR (Mindfulness-based Stress Reduction) | Duloxetine | Total | Acupressure |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 8 Participants | 12 Participants | 51 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 93 Participants | 84 Participants | 349 Participants | 93 Participants |
| Age, Continuous | 51.0 years STANDARD_DEVIATION 13.3 | 50.2 years STANDARD_DEVIATION 10.7 | 50.0 years STANDARD_DEVIATION 11 | 50.2 years STANDARD_DEVIATION 11.8 | 49.0 years STANDARD_DEVIATION 11.9 |
| Annual Household Income $100,000 - $149,999 | 11 Participants | 12 Participants | 13 Participants | 50 Participants | 14 Participants |
| Annual Household Income $10,000 - $24,999 | 15 Participants | 12 Participants | 9 Participants | 48 Participants | 12 Participants |
| Annual Household Income $150,000 - $199,999 | 5 Participants | 9 Participants | 9 Participants | 28 Participants | 5 Participants |
| Annual Household Income $200,000 or more | 5 Participants | 4 Participants | 11 Participants | 24 Participants | 4 Participants |
| Annual Household Income $25,000 - $34,999 | 12 Participants | 10 Participants | 3 Participants | 33 Participants | 8 Participants |
| Annual Household Income $35,000 - $49,999 | 14 Participants | 9 Participants | 9 Participants | 47 Participants | 15 Participants |
| Annual Household Income $50,000 - $74,999 | 11 Participants | 13 Participants | 10 Participants | 50 Participants | 16 Participants |
| Annual Household Income $75,000 - $99,999 | 5 Participants | 12 Participants | 7 Participants | 33 Participants | 9 Participants |
| Annual Household Income Less than $10,000 | 7 Participants | 5 Participants | 9 Participants | 25 Participants | 4 Participants |
| Annual Household Income Prefer not to answer | 16 Participants | 14 Participants | 16 Participants | 58 Participants | 12 Participants |
| Annual Household Income Unknown | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 2 Participants |
| Chronic Pain Acceptance Questionnaire (CPAQ) | 24.6 units on a scale STANDARD_DEVIATION 7.8 | 24.0 units on a scale STANDARD_DEVIATION 8 | 24.1 units on a scale STANDARD_DEVIATION 7.1 | 24.2 units on a scale STANDARD_DEVIATION 7.6 | 24.2 units on a scale STANDARD_DEVIATION 7.5 |
| Education Bachelor's degree | 22 Participants | 23 Participants | 20 Participants | 87 Participants | 22 Participants |
| Education Diploma or equivalent (GED) | 5 Participants | 4 Participants | 8 Participants | 26 Participants | 9 Participants |
| Education Graduate or Professional School diploma | 25 Participants | 24 Participants | 38 Participants | 115 Participants | 28 Participants |
| Education Lower Secondary (Middle School) | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Education Primary (Elementary School) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Education Some College/ Certificate | 36 Participants | 28 Participants | 19 Participants | 109 Participants | 26 Participants |
| Education Some Graduate or Professional School | 4 Participants | 11 Participants | 3 Participants | 24 Participants | 6 Participants |
| Education Unknown | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Education Upper Secondary (High School) | 4 Participants | 5 Participants | 3 Participants | 15 Participants | 3 Participants |
| Education Vocational/Trade School | 6 Participants | 6 Participants | 4 Participants | 22 Participants | 6 Participants |
| Employment Status Full-time employment | 40 Participants | 45 Participants | 43 Participants | 174 Participants | 46 Participants |
| Employment Status Not employed | 20 Participants | 21 Participants | 21 Participants | 80 Participants | 18 Participants |
| Employment Status Part-time employment | 12 Participants | 14 Participants | 17 Participants | 59 Participants | 16 Participants |
| Employment Status Retired | 30 Participants | 21 Participants | 15 Participants | 85 Participants | 19 Participants |
| Employment Status Unknown | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 6 Participants | 26 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 87 Participants | 85 Participants | 345 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 9 Participants | 5 Participants | 29 Participants | 6 Participants |
| Experiences Questionnaire (EQ-11) | 39.8 units on a scale STANDARD_DEVIATION 7.5 | 38.9 units on a scale STANDARD_DEVIATION 7.7 | 40.5 units on a scale STANDARD_DEVIATION 7.4 | 39.6 units on a scale STANDARD_DEVIATION 7.5 | 39.1 units on a scale STANDARD_DEVIATION 7.3 |
| Fear Avoidance Belief Questionnaire (FAPQ) | 15.4 units on a scale STANDARD_DEVIATION 4.9 | 15.9 units on a scale STANDARD_DEVIATION 4.3 | 15.6 units on a scale STANDARD_DEVIATION 5.3 | 15.5 units on a scale STANDARD_DEVIATION 4.9 | 15.1 units on a scale STANDARD_DEVIATION 4.9 |
| Fibromyalgia Criteria | 21 Participants | 20 Participants | 20 Participants | 78 Participants | 17 Participants |
| General Sensitivity Scale (GSS-8) | 2.0 units on a scale STANDARD_DEVIATION 1.9 | 1.7 units on a scale STANDARD_DEVIATION 1.9 | 1.7 units on a scale STANDARD_DEVIATION 1.9 | 1.9 units on a scale STANDARD_DEVIATION 2 | 2.0 units on a scale STANDARD_DEVIATION 2.1 |
| Michigan Body Map | 8.3 number of regions STANDARD_DEVIATION 6.3 | 8.7 number of regions STANDARD_DEVIATION 6.4 | 8.1 number of regions STANDARD_DEVIATION 6.6 | 8.5 number of regions STANDARD_DEVIATION 6.4 | 8.8 number of regions STANDARD_DEVIATION 6.3 |
| Pain Catastrophizing Scale (PCS) | 11.5 units on a scale STANDARD_DEVIATION 5.7 | 12.0 units on a scale STANDARD_DEVIATION 5 | 12.1 units on a scale STANDARD_DEVIATION 6.2 | 12.0 units on a scale STANDARD_DEVIATION 5.6 | 12.4 units on a scale STANDARD_DEVIATION 5.3 |
| PainDetect | 10.9 units on a scale STANDARD_DEVIATION 6.9 | 11.8 units on a scale STANDARD_DEVIATION 7.7 | 11.8 units on a scale STANDARD_DEVIATION 8.1 | 11.5 units on a scale STANDARD_DEVIATION 7.5 | 11.3 units on a scale STANDARD_DEVIATION 7.3 |
| Pain Duration | 133 months STANDARD_DEVIATION 216 | 126 months STANDARD_DEVIATION 183 | 145 months STANDARD_DEVIATION 418 | 129 months STANDARD_DEVIATION 262 | 113 months STANDARD_DEVIATION 155 |
| Pain, Enjoyment of Life, and General Activity (PEG) | 6.4 units on a scale STANDARD_DEVIATION 1.9 | 6.6 units on a scale STANDARD_DEVIATION 1.5 | 6.4 units on a scale STANDARD_DEVIATION 1.9 | 6.4 units on a scale STANDARD_DEVIATION 1.8 | 6.4 units on a scale STANDARD_DEVIATION 1.8 |
| Pain Self Efficacy Questionnaire (PSEQ) | 7.3 units on a scale STANDARD_DEVIATION 3.2 | 7.0 units on a scale STANDARD_DEVIATION 3 | 7.3 units on a scale STANDARD_DEVIATION 3 | 7.1 units on a scale STANDARD_DEVIATION 3.1 | 6.9 units on a scale STANDARD_DEVIATION 3 |
| Perceived Stress Scale (PSS) | 5.8 units on a scale STANDARD_DEVIATION 3.1 | 6.2 units on a scale STANDARD_DEVIATION 3.4 | 6.0 units on a scale STANDARD_DEVIATION 3.4 | 6.1 units on a scale STANDARD_DEVIATION 3.3 | 6.2 units on a scale STANDARD_DEVIATION 3.4 |
| Positive and Negative Affect Scale (PANAS) Negative Affect | 19.3 units on a scale STANDARD_DEVIATION 7.1 | 20.3 units on a scale STANDARD_DEVIATION 7.6 | 18.7 units on a scale STANDARD_DEVIATION 7.5 | 19.9 units on a scale STANDARD_DEVIATION 7.7 | 21.3 units on a scale STANDARD_DEVIATION 8.5 |
| Positive and Negative Affect Scale (PANAS) Positive Affect | 31.0 units on a scale STANDARD_DEVIATION 8.6 | 31.1 units on a scale STANDARD_DEVIATION 8 | 31.6 units on a scale STANDARD_DEVIATION 8.4 | 31.0 units on a scale STANDARD_DEVIATION 8.3 | 30.5 units on a scale STANDARD_DEVIATION 8.1 |
| PROMIS Anxiety | 7.7 units on a scale STANDARD_DEVIATION 3.5 | 8.0 units on a scale STANDARD_DEVIATION 3.5 | 8.0 units on a scale STANDARD_DEVIATION 4.1 | 8.1 units on a scale STANDARD_DEVIATION 3.8 | 8.6 units on a scale STANDARD_DEVIATION 4.2 |
| PROMIS Cognitive Function | 7.2 units on a scale STANDARD_DEVIATION 1.9 | 7.3 units on a scale STANDARD_DEVIATION 2 | 7.2 units on a scale STANDARD_DEVIATION 2.3 | 7.2 units on a scale STANDARD_DEVIATION 2 | 7.1 units on a scale STANDARD_DEVIATION 1.9 |
| PROMIS Depression | 8.1 units on a scale STANDARD_DEVIATION 3.9 | 8.3 units on a scale STANDARD_DEVIATION 3.8 | 7.8 units on a scale STANDARD_DEVIATION 3.8 | 8.2 units on a scale STANDARD_DEVIATION 3.9 | 8.6 units on a scale STANDARD_DEVIATION 4.3 |
| PROMIS Fatigue | 12.3 units on a scale STANDARD_DEVIATION 4.5 | 12.3 units on a scale STANDARD_DEVIATION 4.4 | 11.9 units on a scale STANDARD_DEVIATION 4.6 | 12.3 units on a scale STANDARD_DEVIATION 4.5 | 12.9 units on a scale STANDARD_DEVIATION 4.6 |
| PROMIS Pain Intensity | 6.4 units on a scale STANDARD_DEVIATION 1.7 | 6.4 units on a scale STANDARD_DEVIATION 1.5 | 6.3 units on a scale STANDARD_DEVIATION 1.9 | 6.3 units on a scale STANDARD_DEVIATION 1.7 | 6.1 units on a scale STANDARD_DEVIATION 1.6 |
| PROMIS Pain Interference | 14.9 units on a scale STANDARD_DEVIATION 3.5 | 15.5 units on a scale STANDARD_DEVIATION 3 | 14.8 units on a scale STANDARD_DEVIATION 3.4 | 15.0 units on a scale STANDARD_DEVIATION 3.3 | 14.8 units on a scale STANDARD_DEVIATION 3.2 |
| PROMIS Physical Function | 17.3 units on a scale STANDARD_DEVIATION 4.9 | 16.8 units on a scale STANDARD_DEVIATION 4.1 | 17.8 units on a scale STANDARD_DEVIATION 5.3 | 17.3 units on a scale STANDARD_DEVIATION 4.7 | 17.5 units on a scale STANDARD_DEVIATION 4.7 |
| PROMIS Sleep Disturbance | 19.4 units on a scale STANDARD_DEVIATION 5.6 | 19.1 units on a scale STANDARD_DEVIATION 5.8 | 20.2 units on a scale STANDARD_DEVIATION 5.4 | 19.5 units on a scale STANDARD_DEVIATION 5.5 | 19.4 units on a scale STANDARD_DEVIATION 5.2 |
| PROMIS Social Roles and Activities | 11.4 units on a scale STANDARD_DEVIATION 3.9 | 11.3 units on a scale STANDARD_DEVIATION 3.6 | 11.7 units on a scale STANDARD_DEVIATION 4.1 | 11.4 units on a scale STANDARD_DEVIATION 3.8 | 11.3 units on a scale STANDARD_DEVIATION 3.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 10 Participants | 16 Participants | 40 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 16 Participants | 27 Participants | 88 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 6 Participants | 7 Participants | 26 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 2 Participants | 16 Participants | 6 Participants |
| Race (NIH/OMB) White | 66 Participants | 64 Participants | 44 Participants | 228 Participants | 54 Participants |
| Region of Enrollment United States | 102 participants | 101 participants | 96 participants | 400 participants | 101 participants |
| Relationship Status Divorced | 18 Participants | 19 Participants | 14 Participants | 75 Participants | 24 Participants |
| Relationship Status Married | 47 Participants | 55 Participants | 55 Participants | 205 Participants | 48 Participants |
| Relationship Status Never married | 31 Participants | 23 Participants | 18 Participants | 93 Participants | 21 Participants |
| Relationship Status Separated | 1 Participants | 1 Participants | 3 Participants | 8 Participants | 3 Participants |
| Relationship Status Unknown | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Relationship Status Widowed | 5 Participants | 3 Participants | 6 Participants | 18 Participants | 4 Participants |
| Sex: Female, Male Female | 68 Participants | 72 Participants | 63 Participants | 273 Participants | 70 Participants |
| Sex: Female, Male Male | 34 Participants | 29 Participants | 33 Participants | 127 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 182 | 0 / 175 | 0 / 202 | 0 / 282 | 0 / 494 | 1 / 405 |
| other Total, other adverse events | 1 / 182 | 1 / 175 | 0 / 202 | 40 / 282 | 4 / 494 | 2 / 405 |
| serious Total, serious adverse events | 5 / 182 | 8 / 175 | 6 / 202 | 3 / 167 | 9 / 494 | 17 / 405 |
Outcome results
Primary
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3)
The PROMIS pain interference consists of 4 questions on a Likert scale ranging from 'Not at all (1) to Very much (5). Total scores are between 4 and 20, with higher scores indicating increased pain interference.
Time frame: week 6 (T2), week 15 (T3)
Population: Of the 402 participants who were randomized to a treatment, 331 who completed the T3 study visit were analyzed. Participants excluded from this analysis are those who did not complete either T2 or T3.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MBSR (mindfulness-based stress reduction) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3) | -0.9 score on a scale |
| PT and exercise | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3) | -1.8 score on a scale |
| Acupressure | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3) | -1.6 score on a scale |
| Duloxetine | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a Between Week 6 (T2) to Week 15 (T3) | -2.0 score on a scale |
Secondary
Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3)
This is a 3 question scale where participants select a between 0 (no pain) to 10 (pain is bad and completely interferes). Higher the scores the worse the pain.
Time frame: week 6 (T2), week 15 (T3)
Population: Of the 402 randomized participants, 331 who completed T3 study visit were analyzed. Participants excluded from this analysis are those who did not complete either T2 or T3.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MBSR (mindfulness-based stress reduction) | Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3) | -1.0 score on a scale |
| PT and exercise | Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3) | -1.5 score on a scale |
| Acupressure | Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3) | -0.5 score on a scale |
| Duloxetine | Change in the Pain, Enjoyment, and General Activity Scale (PEG) From Week 6 (T2) to Week 15 (T3) | -1.2 score on a scale |
Secondary
Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3)
This is a 1 question item where participants described their perceived improvement between T2 and T3 by selecting a score between 1 and 7, where 1 indicated very much improved and 7 indicated very much worse. The lower the score, the greater improvement in perceived pain. Data is presented as count of participants who scored their improvement as a 1 or a 2 and those who scored their improvement as 3 or higher.
Time frame: week 15 (T3)
Population: Of the 402 randomized participants, 331 who completed T3 study visit were analyzed. Participants excluded from this analysis are those who did not complete either T2 or T3.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MBSR (mindfulness-based stress reduction) | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Very much (score of 1) /much improved (score of 2) | 4 Participants |
| MBSR (mindfulness-based stress reduction) | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Score 3 or higher | 75 Participants |
| PT and exercise | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Score 3 or higher | 55 Participants |
| PT and exercise | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Very much (score of 1) /much improved (score of 2) | 35 Participants |
| Acupressure | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Very much (score of 1) /much improved (score of 2) | 21 Participants |
| Acupressure | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Score 3 or higher | 58 Participants |
| Duloxetine | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Very much (score of 1) /much improved (score of 2) | 21 Participants |
| Duloxetine | Patient Global Impression of Change (PGIC) From Week 6 (T2) to Week 15 (T3) | Score 3 or higher | 62 Participants |