QUANTIFY: Quantitative Understanding of Advanced Novel Techniques for Imaging Fasciitis and Yielding Biomarkers (QUANTIFY)

This study is to create a test that can accurately find and measure the problem areas in muscle and fascia tissue, also known as myofascial pain. The hypothesis is that a combination of imaging findings will be able to detect when myofascial pain is present. The goal is to improve management of myofascial pain by making better tools to find changes in the muscle and fascia tissues for a more personalized treatment. This project was funded by the HEAL initiative (https://heal.nih.gov/).

Study Overview

• Status: Recruiting
• Conditions: Achilles Tendinopathy; Plantar Fasciopathy; Controls
• Intervention / Treatment: Diagnostic test: Clinical exam; Diagnostic test: Ultrasound imaging; Diagnostic test: Magnetic Resonance Imaging

Detailed Description

The objective of the R61 phase is to use novel imaging techniques to develop a diagnostic biosignature to objectively and accurately determine the location and severity of abnormal myofascial tissue. A cross-sectional study design approach with 3 groups: plantar fasciitis (n=50), Achilles tendinopathy (n=25), and pain-free controls (n=25) to test Specific Aim: Develop a diagnostic imaging biosignature of myofascial tissue to differentiate individuals with plantar fasciitis from other foot pain without a myofascial component (Achilles tendinopathy) and from matched pain-free controls.

The goal is to develop a diagnostic imaging biosignature that will be able to distinguish between A-MTrP in individuals with plantar fasciitis compared to healthy tissue control (pain-free controls). The biosignature developed in this R61 phase will be screened for clinical utility and considered of interest for further study if it meets the following milestone criteria: area under the receiver operating characteristic curve (ROC AUC) >0.7, sensitivity >60%, and specificity >60%. The ROC analysis will estimate diagnostic performance by comparing differences in biosignatures between tissue where myofascial pain is present vs. tissue where pain is absent.

The proposed sample size of 50 individuals with plantar fasciitis, 25 individuals with Achilles tendinopathy, and 25 matched controls was chosen to provide a confidence interval halfwidth of 0.10 for an AUC of 0.70, assuming 5 muscle measurements for each participant and an overall A-MTrPs prevalence of 0.36 in individuals with plantar fasciitis. Further assuming the 20 biomarkers to be considered in the R61 phase have AUCs uniformly distributed from 0.5 to 0.8, will have at least 85% power to obtain a biosignature meeting the milestone criteria.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jing Danielson, DDS; Phone Number: 319-356-1722; Email: chimenti-lab@uiowa.edu
• Study Contact Backup: Name: Jessica Danielson, DDS; Phone Number: 319-356-9791; Email: chimenti-lab@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Health Care
      • Contact: Jessica Danielson, DDS; Phone Number: 319-335-9791; Email: Chimenti-lab@uiowa.edu
      • Contact: Jessica Danielson, DDS; Phone Number: 319-356-1722; Email: jessica-danielson@uiowa.edu
      • Principal Investigator: Ruth L Chimenti, PT, PhD
      • Principal Investigator: Kathleen A Sluka, PT, PhD
      • Principal Investigator: James Holmes, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria for plantar fasciitis group:

• Clinical diagnosis of plantar fasciitis
• Duration of plantar fasciitis pain greater than or equal to 3 months
• Severity of plantar fasciitis pain greater than or equal to 3/10

Inclusion criteria for Achilles tendinopathy group:

• Clinical diagnosis of insertional Achilles tendinopathy:
• Duration of Achilles tendinopathy pain greater than or equal to 3 months
• Severity of Achilles tendon pain greater than or equal to 3/10

Control group:

• Similar age, sex, and BMI as plantar fasciitis and Achilles tendinopathy groups

Exclusion criteria:

• Younger than 18 years of age
• History of an invasive procedures to the foot and ankle on the side of interest
• History of lower extremity injections, dry needling, or EPAT/ESWT within past 3 months on the side of interest
• Contraindications for MRI (e.g. non-MR compatible implanted devices, claustrophobia, inability to remain still comfortably for 1 hour in a supine position, body size too large for MR scanner)
• Clinically unstable medical or psychiatric issues
• Pregnant or possibly pregnant
• Co-morbidities associated with changes in musculoskeletal imaging, including: Diagnosed systemic conditions affecting the foot and ankle (e.g., rheumatoid arthritis, spondyloarthropathy, gout) endocrine disorder with complications (e.g., uncontrolled Type I or II diabetes, diabetic peripheral neuropathy) Neuromuscular diseases (e.g., Charcot-Marie-Tooth (CMT) disease) Connective tissue disorder (e.g. Marfan's syndrome, Ehlers-Danlos) Osteoarthritis of the foot or ankle History of foot or ankle fracture Infection of the foot or ankle (e.g., infectious fasciitis, calcaneal osteomyelitis) within the past year Familial hypercholesterolemia Neoplasms involving the foot, Plantar fibromatosis
• Control group only: Persistent or recurrent leg pain in the past 6 months
• Plantar fasciitis and Achilles tendinopathy groups only: Other source of heel or foot pain (e.g., tarsal tunnel syndrome, peripheral neuropathy, lumbar radiculopathy, calcaneal stress fracture, Morton's neuroma, fibromyalgia) or co-occurring plantar fasciitis and Achilles tendinopathy (for the Achilles tendinopathy group).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Diagnostic imaging; All participants will have a clinical exam, magnetic resonance imaging, and ultrasound imaging of their foot and ankle.

Diagnostic test: Clinical exam; An experienced physical therapist with expertise in dry needling will confirm study eligibility and complete a standard clinical exam for myofascial pain. Gold standard for diagnosing myofascial pain as defined by Travell and Simons will be used. The criteria for muscle trigger point (TrP) include: 1) a taut band of skeletal muscle that is tender to palpation, 2) sustained compression of the taut band reproduces or exacerbates the participant's symptoms. Healthy tissue is defined as no palpable taut band.; Diagnostic test: Ultrasound imaging; Shear wave elastography and b-mode ultrasound imaging techniques will capture the biomechanical and structural profile of foot and ankle muscle on the involved side.; Diagnostic test: Magnetic Resonance Imaging; T1rho and IDEAL sequences will be used to capture the biochemical and structural profile of foot and ankle muscles on the involved side

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Reference Test: Trigger point (TrP)	Travell and Simons' criteria will be used to identify active muscle trigger points (TrPs) as present or absent. The score will be "Yes" for present and "No" for absent.	Enrollment
Diagnostic Index Test: Imaging biosignature	The biosignature will include a combination of ultrasound and/or magnetic resonance imaging measures to capture biomechanical, biochemical, and structural profile of myofascial tissue. Current key candidate imaging biomarkers include: T1p of muscle and fascia, Elastic modulus of the muscle, Shear strain of the plantar fascia, Fat fraction of the muscle, and Thickness of the plantar fascia. The is currently no established scale for this biosignature, which will be developed as part of this study.	Enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity and Interference	The PEG (Pain, Enjoyment, General activity) is a three-item scale to assess pain intensity and interference. Each question is rated from 0 (least) to 10 (worst) and the scores are averaged to calculate a total PEG score.	Enrollment
Movement-evoked pain	Participants will rate their pain using a verbal numeric rating scale (0-10) during walking where "0" represents "no pain" and "10" represents "worst pain imaginable"	Enrollment
Physical Function	Participants will report their level of physical function using the PROMIS (Patient-Reported Outcomes Measurement Information System) Physical Function, Short form 6b. For PROMIS measures the general population mean is 50 with a standard deviation of 10. Impaired physical function would be indicated by a score less than 40.	Enrollment

Collaborators and Investigators

• Sponsor: Ruth Chimenti
• Collaborators: National Center for Complementary and Integrative Health (NCCIH); Rochester Institute of Technology
• Investigators: Principal Investigator: Ruth L Chimenti, PT, PhD, University of Iowa; Principal Investigator: Kathleen Sluka, PT, PhD, University of Iowa; Principal Investigator: James Holmes, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: January 26, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; pain; biomarker; ultrasound imaging; myofascial; plantar fasciitis; achilles tendinitis
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Foot Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fasciitis; Pain; Fasciitis, Plantar; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging; Ultrasonography
• Other Study ID Numbers: 202409110; R61AT012275 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data that is necessary to validate primary outcomes and publications will be preserved and shared to allow other researchers the ability to reproduce the data and obtain additional findings that can advance the results. To ensure that other users can efficiently and accurately use the dataset, as well as to prevent misinterpretation or misuse, we will provide metadata and associated documentation. Information needed to understand the meaning of variable names and information about coding for missing data will be recorded in data dictionaries and readme files that will subsequently be shared alongside final datasets. Protocols, methods, statistical analyses, and any other relevant documentation derived from notes during data collection will be incorporated into readme files that will accompany the data when shared.
• IPD Sharing Time Frame: IPD will be available within 1 year of completing the study or upon publication, whichever occurs first. The data will remain available for at least 10 years. The primary outcome data and accompanying metadata will be deposited into an NIH Helping End Addiction Long-term (HEAL) compliant data repository.

IPD Sharing Access Criteria

The primary outcome data and accompanying metadata will be deposited into an NIH Helping End Addiction Long-term (HEAL) compliant data repository. In accordance with International Committee of Medical Journal Editors (ICMJE), we will prepare the primary analysis datasets for review and reproducibility by peer-reviewed journals.

Publications will be made available to the public using open access publishing, so that they become immediately available to the public. All publications will be accessible through PubMed, Google Scholar, and through open access.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes