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Chronic Musculoskeletal PainNCT04994249

Diagnostic and Prognostic Biomarkers for High-impact Chronic Pain: Development and Validation

An observational study of Chronic Musculoskeletal Pain and Pain, run by Stanford University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

To identify diagnostic and prognostic biomarker signatures of recovery versus having persisting high-impact chronic pain and functional disability in adults with Chronic Musculoskeletal Pain. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Musculoskeletal Pain, Pain, Pain, Chronic
How many people
250 participants
Where
1 siteUnited States
Study dates
21 Mar 2022to 31 Dec 2027
Phase
Observational
Are there results?
Not yet: the study is under way

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Musculoskeletal high-impact chronic pain.

Who may be able to join

  • 1) Inclusion criteria: Adults (18-80 years; ~64% female expected based on clinic distribution) with chronic MSP as categorized by the World Health Organization (WHO).

Who cannot join

  • 1) Chronic musculoskeletal pain (MSP) explained by inflammatory disease (e.g., rheumatoid arthritis, lupus) or CP with a primary diagnosis other than chronic MSP (e.g., neuropathic pain), (2) significant cognitive impairment, (3) MRI contraindication, (4) medical or psychiatric problems interfering with the study, (5) current medicolegal factors (e.g., open disability claim), (6) plans for surgery during the study, (7) pregnancy and (8) Children under the age of 18 will not be included in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University

    Palo Alto, California, 94304

Other trials in United States

About this study

To identify diagnostic and prognostic biomarker signatures of recovery versus having persisting high-impact chronic pain and functional disability in adults with Chronic Musculoskeletal Pain.

Read the detailed description

Our overall goal is to discover and validate diagnostic and prognostic biomarkers for musculoskeletal high-impact chronic pain. Chronic pain represents a public health crisis that affects 50-100 million Americans and costs over $500 billion dollars annually. Chronic musculoskeletal pain conditions comprise 70-80% of all chronic pain. The highest-need and most impacted patients are those with high-impact chronic pain (affecting ~20 million Americans), or pain associated with substantially restricted work, social, and self-care activities for six or more months. Chronic pain-and high-impact chronic pain in particular-is often treated with prescription opioids, and is linked to opioid-use disorder. Multidisciplinary chronic pain treatments show incomplete recovery at the population level. However, subgroups of individuals completely respond, do not change, or even worsen following pain management. Thus, robust and validated diagnostic and prognostic biomarkers are needed to identify those with high-impact chronic pain and determine the trajectory of outcome (i.e., recovery versus persistence), respectively. Such biomarkers are essential to develop safer, more effective patient-specific treatment strategies, particularly for those who are refractory to current treatment options.

Many factors have been shown to be (1) diagnostic for the severity and impact of chronic pain or (2) prognostic of the trajectory of chronic pain, including those that are related to the central nervous system (CNS; structure, function), psychosocial (e.g., anxiety, catastrophizing, social isolation), sensory (e.g., temporal summation, conditioned pain modulation),1functional (e.g., accelerometry), multiomic (e.g., immune, microbiome), and demographic. However, these studies are limited by (1) association rather than predictive validity; (2) small sample sizes; (3) homogenous populations limiting external validity; and (4) single modality factors. As chronic pain is a biopsychosocial condition, the investigator will need to measure broadly across these multiple dimensions; the most valuable insights will be gained by understanding not only individual pieces of data, but the relationships among them. Recognizing the critical need for rapid, valid, and clinically useful breakthroughs in signature discovery for risk- and treatment-stratification and novel therapeutic targets for chronic pain, as called for in the HEAL initiative, the investigator's aim is to discover reliable, validated diagnostic and prognostic biomarker signatures of musculoskeletal high-impact chronic pain by integrating CNS, multiomic, sensory, functional, psychosocial, and demographic domains.

Keywords
Pain
Medical subject headings
Pain, Chronic Pain, Arthralgia

What is being measured

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

  1. Pain Interference:

    Pain Interference using Patient-Reported Outcome Measurement Information System (PROMIS)-Pain Interference on a T score (mean: 50; standard deviation: 10) and Graded Chronic Pain Scale (GCPS)

    Measured: 6 months after baseline assessment

Timeline

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

  1. First posted6 Aug 2021
  2. Study start21 Mar 2022
  3. Primary completion25 Apr 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04994249
Sponsor's protocol ID
60657
Other IDs
1R61NS118651-01A1
Status last verified
Feb 2026
First submitted
29 Jul 2021
Last updated
20 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Von Korff M, Scher AI, Helmick C, Carter-Pokras O, Dodick DW, Goulet J, Hamill-Ruth R, LeResche L, Porter L, Tait R, Terman G, Veasley C, Mackey S. United States National Pain Strategy for Population Research: Concepts, Definitions, and Pilot Data. J Pain. 2016 Oct;17(10):1068-1080. doi: 10.1016/j.jpain.2016.06.009. Epub 2016 Jul 1.

    PubMed 27377620

  • Kutch JJ, Labus JS, Harris RE, Martucci KT, Farmer MA, Fenske S, Fling C, Ichesco E, Peltier S, Petre B, Guo W, Hou X, Stephens AJ, Mullins C, Clauw DJ, Mackey SC, Apkarian AV, Landis JR, Mayer EA; MAPP Research Network. Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study. Pain. 2017 Jun;158(6):1069-1082. doi: 10.1097/j.pain.0000000000000886.

    PubMed 28328579

  • Ung H, Brown JE, Johnson KA, Younger J, Hush J, Mackey S. Multivariate classification of structural MRI data detects chronic low back pain. Cereb Cortex. 2014 Apr;24(4):1037-44. doi: 10.1093/cercor/bhs378. Epub 2012 Dec 17.

    PubMed 23246778

  • Brown JE, Chatterjee N, Younger J, Mackey S. Towards a physiology-based measure of pain: patterns of human brain activity distinguish painful from non-painful thermal stimulation. PLoS One. 2011;6(9):e24124. doi: 10.1371/journal.pone.0024124. Epub 2011 Sep 13.

    PubMed 21931652

  • Feinstein AB, Sturgeon JA, Darnall BD, Dunn AL, Rico T, Kao MC, Bhandari RP. The Effect of Pain Catastrophizing on Outcomes: A Developmental Perspective Across Children, Adolescents, and Young Adults With Chronic Pain. J Pain. 2017 Feb;18(2):144-154. doi: 10.1016/j.jpain.2016.10.009. Epub 2016 Nov 5.

    PubMed 27825857

  • Bhandari RP, Feinstein AB, Huestis SE, Krane EJ, Dunn AL, Cohen LL, Kao MC, Darnall BD, Mackey SC. Pediatric-Collaborative Health Outcomes Information Registry (Peds-CHOIR): a learning health system to guide pediatric pain research and treatment. Pain. 2016 Sep;157(9):2033-2044. doi: 10.1097/j.pain.0000000000000609.

    PubMed 27280328

  • Sharifzadeh Y, Kao MC, Sturgeon JA, Rico TJ, Mackey S, Darnall BD. Pain Catastrophizing Moderates Relationships between Pain Intensity and Opioid Prescription: Nonlinear Sex Differences Revealed Using a Learning Health System. Anesthesiology. 2017 Jul;127(1):136-146. doi: 10.1097/ALN.0000000000001656.

    PubMed 28614083

  • Karayannis NV, Baumann I, Sturgeon JA, Melloh M, Mackey SC. The Impact of Social Isolation on Pain Interference: A Longitudinal Study. Ann Behav Med. 2019 Jan 1;53(1):65-74. doi: 10.1093/abm/kay017.

    PubMed 29668841

  • Sturgeon JA, Dixon EA, Darnall BD, Mackey SC. Contributions of physical function and satisfaction with social roles to emotional distress in chronic pain: a Collaborative Health Outcomes Information Registry (CHOIR) study. Pain. 2015 Dec;156(12):2627-2633. doi: 10.1097/j.pain.0000000000000313.

    PubMed 26230739

  • Goodin BR, Bulls HW, Herbert MS, Schmidt J, King CD, Glover TL, Sotolongo A, Sibille KT, Cruz-Almeida Y, Staud R, Fessler BJ, Redden DT, Bradley LA, Fillingim RB. Temporal summation of pain as a prospective predictor of clinical pain severity in adults aged 45 years and older with knee osteoarthritis: ethnic differences. Psychosom Med. 2014 May;76(4):302-10. doi: 10.1097/PSY.0000000000000058.

    PubMed 24804882

Questions about this trial

What is this clinical trial studying?

An observational study of Chronic Musculoskeletal Pain and Pain, run by Stanford University at 1 site in United States.

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 1 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Pain Interference: (time frame: 6 months after baseline assessment). 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 NCT04994249, which also lists 10 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 20 Feb 2026.

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