The Back Pain Consortium Research Program Study

Chronic Low-back Pain Clinical Trial

— BACPAC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04870957
• Other study ID #: HUM00180994
• Secondary ID: 1U19AR076734-01
• Status: Recruiting
• Phase: Phase 4
• Start date: June 9, 2021
• Est. completion date: June 2027

Study information

• Verified date: November 2023
• Source: University of Michigan
• Contact: Sana Shaikh
• Phone: 734-763-5226
• Email: BACPACstudy[@]med.umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Back Pain
• Chronic Low-back Pain
• Low Back Pain

Intervention

Behavioral:
• PainGuide
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.
• 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.
• 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.

Device:
• 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.

Drug:
• 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.

Device:
• 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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	week 6 (T2), week 15 (T3)
Secondary	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.	week 6 (T2), week 15 (T3)
Secondary	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.	week 6 (T2), week 15 (T3)