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The Back Pain Consortium Research Program Study (BACPAC)

Primary Purpose

Chronic Low-back Pain

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

PainGuide

MBSR

PT and exercise

Self -administered acupressure

Duloxetine

Pro-Diary monitor

About this trial

This is an interventional treatment trial for Chronic Low-back Pain focused on measuring Pain, Back Pain

Eligibility Criteria

25 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Exclusion Criteria for Deep Phenotyping (subset 160 participants):

Severe claustrophobia precluding MRI and evoked pain testing during scanning
Diagnosed peripheral neuropathy
Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail)
Body Mass Index greater than 45 or unable to comfortably fit in the bore of the MRI magnet

Sites / Locations

University of MichiganRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm Type

Experimental

Arm Label

MBSR (mindfulness-based stress reduction)

PT and exercise

Acupressure

Duloxetine

MBSR then PT and exercise

MBSR then Acupressure

MBSR then Duloxetine

PT and exercise then MBSR

PT and exercise then Acupressure

PT and exercise then Duloxetine

Acupressure then MBSR

Acupressure then PT and exercise

Acupressure then Duloxetine

Duloxetine then MBSR

Duloxetine then PT and exercise

Duloxetine then Acupressure

PainGuide

Arm Description

Run-in treatment then MBSR.

Run-in treatment then PT and exercise

Run-in treatment then Acupressure

Run-in treatment then Duloxetine

Run-in treatment then 8 weeks of MBSR, and then 8 weeks of PT and exercise.

Run-in treatment, then 8 weeks of MBSR, and then 8 weeks Acupressure.

Run-in treatment, then 8 weeks of MBSR, and then approximately 8 weeks of Duloxetine

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of MBSR.

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of Acupressure

Run-in treatment, then 8 weeks of PT and exercise, and then approximately 8 weeks of Duloxetine

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of MBSR

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of PT and exercise.

Run-in treatment, then 8 weeks of Acupressure, and then approximately 8 weeks of Duloxetine

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of MBSR.

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of PT and exercise

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks Acupressure.

Run-in treatment only with no additional treatments.

Outcomes

Primary Outcome Measures

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference 4a between week 6 to week 15

The PROMIS pain interference consists of 4 questions on a Likert scale ranging from 'Not at all" (1) to "Very much" (5), with higher scores indicating increased pain interference.

Secondary Outcome Measures

Change in the Pain, Enjoyment, and General Activity Scale (PEG) from week 6 to week 15

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.

Change in Patient Global Impression of Change (PGIC) from week 6 to week 15

This is a 1 question item where participants select very much improved (1) to very much worse (7). The lower the score the less pain.

Full Information

NCT ID

NCT04870957

First Posted

April 28, 2021

Last Updated

December 5, 2022

Sponsor

University of Michigan

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

1. Study Identification

Unique Protocol Identification Number

NCT04870957

Brief Title

The Back Pain Consortium Research Program Study

Acronym

BACPAC

Official Title

University of Michigan Mechanistic Research Center -The Back Pain Consortium Research Program

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 9, 2021 (Actual)

Primary Completion Date

June 2027 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Low-back Pain

Keywords

Pain, Back Pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Sequential Assignment

Model Description

Sequential, multiple assignment, randomized trial (SMART) design

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MBSR (mindfulness-based stress reduction)

Arm Type

Experimental

Arm Description

Run-in treatment then MBSR.

Arm Title

PT and exercise

Arm Type

Experimental

Arm Description

Run-in treatment then PT and exercise

Arm Title

Acupressure

Arm Type

Experimental

Arm Description

Run-in treatment then Acupressure

Arm Title

Duloxetine

Arm Type

Experimental

Arm Description

Run-in treatment then Duloxetine

Arm Title

MBSR then PT and exercise

Arm Type

Experimental

Arm Description

Run-in treatment then 8 weeks of MBSR, and then 8 weeks of PT and exercise.

Arm Title

MBSR then Acupressure

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of MBSR, and then 8 weeks Acupressure.

Arm Title

MBSR then Duloxetine

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of MBSR, and then approximately 8 weeks of Duloxetine

Arm Title

PT and exercise then MBSR

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of MBSR.

Arm Title

PT and exercise then Acupressure

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of Acupressure

Arm Title

PT and exercise then Duloxetine

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of PT and exercise, and then approximately 8 weeks of Duloxetine

Arm Title

Acupressure then MBSR

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of MBSR

Arm Title

Acupressure then PT and exercise

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of PT and exercise.

Arm Title

Acupressure then Duloxetine

Arm Type

Experimental

Arm Description

Run-in treatment, then 8 weeks of Acupressure, and then approximately 8 weeks of Duloxetine

Arm Title

Duloxetine then MBSR

Arm Type

Experimental

Arm Description

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of MBSR.

Arm Title

Duloxetine then PT and exercise

Arm Type

Experimental

Arm Description

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of PT and exercise

Arm Title

Duloxetine then Acupressure

Arm Type

Experimental

Arm Description

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks Acupressure.

Arm Title

PainGuide

Arm Type

Experimental

Arm Description

Run-in treatment only with no additional treatments.

Intervention Type

Behavioral

Intervention Name(s)

PainGuide

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

MBSR

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

PT and exercise

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Self -administered acupressure

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Duloxetine

Other Intervention Name(s)

Cymbalta

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Pro-Diary monitor

Other Intervention Name(s)

Electronic wrist device that looks like a watch

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference 4a between week 6 to week 15

Description

The PROMIS pain interference consists of 4 questions on a Likert scale ranging from 'Not at all" (1) to "Very much" (5), with higher scores indicating increased pain interference.

Time Frame

week 6 (T2), week 15 (T3)

Secondary Outcome Measure Information:

Title

Change in the Pain, Enjoyment, and General Activity Scale (PEG) from week 6 to week 15

Description

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)

Title

Change in Patient Global Impression of Change (PGIC) from week 6 to week 15

Description

This is a 1 question item where participants select very much improved (1) to very much worse (7). The lower the score the less pain.

Time Frame

week 6 (T2), week 15 (T3)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 Exclusion Criteria for Deep Phenotyping (subset 160 participants): Severe claustrophobia precluding MRI and evoked pain testing during scanning Diagnosed peripheral neuropathy Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail) Body Mass Index greater than 45 or unable to comfortably fit in the bore of the MRI magnet

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sana Shaikh

Phone

734-763-5226

BACPACstudy@med.umich.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Afton Hassett, PsyD

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Daniel Clauw, MD

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48170

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sana Shaikh

Phone

734-232-0882

skazi@med.umich.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data (including bio-specimens, omic data, raw imaging data, and other study data) will be shared with consortial partners. Data will be held at a Data Acquisition Center (DAC) hosted at the University of North Carolina. Omics data will be shared through NIH portals as required. Data dictionaries are harmonized across study sites and shared with consortial partners.

IPD Sharing Time Frame

Per the study data sharing plan, data will be shared to the consortial DAC at fixed intervals after 20% completion is attained (and then at each subsequent 20%). The consortium currently plans for perpetual access for consortial partners.

IPD Sharing Access Criteria

The data will be available only to members of the consortium and is governed by a consortial data use agreement. Members must submit a request form for data access. The Data Access and Publications Committee will review requests and notify Data Access Team when access can be granted.

Learn more about this trial

The Back Pain Consortium Research Program Study

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