DFC 004 Biomarkers for Active Diabetic Foot Ulcers

Predictive and Diagnostic Biomarkers for Diabetic Foot Ulcers: Open Wound Master Study

This study is a platform study designed to efficiently test multiple biomarkers to identify diabetic foot ulcers (DFUs) with a higher potential for healing versus not healing that ultimately could be applied at the point of care to drive personalized management decisions, and to better inform clinical trials of wound healing interventions

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Diabetic Foot; Diabetic Foot Ulcer

Detailed Description

This study is a platform study designed to efficiently test multiple biomarkers to identify diabetic foot ulcers (DFUs) with a higher potential for healing versus not healing that ultimately could be applied at the point of care to drive personalized management decisions, and to better inform clinical trials of wound healing interventions The platform study is designed to be flexible so that it is suitable for a wide range of studies relevant to patients with open (active) DFUs.

This platform study will enroll patients with DFUs seen in an outpatient setting in diabetic foot and wound care clinics across a range of healthcare systems, including community settings and tertiary care hospitals, participating in the DFC.

The platform study will include common procedures that are applicable across the entire spectrum of DFUs (e.g., uniform biospecimen collections, clinical and usual care characteristics, social determinants of health, and patient reported outcomes). Blood, wound fluid (by a variety of methods), wound dressings, and debridement tissue (if debridement is performed during the participant's clinical wound care) will be collected from all participants to support a biorepository for concurrent and future research. Urine samples will be collected if participants agree to provide them, and collection will be encouraged. Biomarker-specific studies requiring additional data or biospecimens not required in the platform study will be included as appendices, as needed. Other biomarker-specific studies that use platform study biospecimens and study data will follow the DFC ancillary study process.

Eligible participants enrolled in the master protocol who signed the informed consent may be enrolled in multiple biomarkers sub studies associated with the master protocol without the need to sign an additional informed consent.

This platform study is non-interventional; no study prescribed agents or therapies are administered.

Eligible and consented participants are managed at each DFC site according to the usual clinical care, which is expected to be in line with the current standards of care recommendations1-3. The study will collect relevant details regarding the care provided at each clinic visit and participant outcomes.

Follow-up for participants will vary based upon the occurrence and timing of healing:

• All participants will be followed every other week for one month and monthly thereafter until the wound is healed or week 52 if the wound has not healed.
• Participants who experience wound healing prior to week 52 will have a confirmation visit 2 weeks later. These participants will also be assessed for recurrence of their DFU at weeks 52 and 78 via phone call or video visit.
• Participants who experience wound healing at week 52 will have a confirmation visit 2 weeks later. These participants will also be assessed for recurrence of their DFU at week 78 via phone call or video visit.
• Participants who do not experience wound healing by week 52 will have an additional phone call or video visit scheduled at week 78 to assess patient-reported wound healing, infection, or amputation with confirmation by electronic medical records (EMR), if available.

Study visits may occur in conjunction with the participant's scheduled clinical follow-up visits. After wound healing has been confirmed, the visit may be conducted by remote means.

The master protocol will enable evaluation of the time to healing over a 78-week period and of expectations on the natural history of wound healing in contemporary DFU participants. It also enables exploring rates of DFU recurrence in those who healed. These data will lead to more accurate DFU-specific standards of care guidelines that will have a direct impact and benefit in the clinical care, for a personalized approach.

General and biomarker-specific analyses will be performed. Participants who share common demographic or clinical characteristics may be pooled across substudies.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona College of Medicine
      • Principal Investigator: Geoffrey Gurtner, MD
      • Contact: Fleur Maturo; Phone Number: 520-621-8296; Email: fleurmartinez@arizona.edu
  • California
    • Los Angeles, California, United States, 90033
      • Active, not recruiting
      • University of Southern California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California - San Francisco
      • Principal Investigator: Michael Conte, MD
      • Contact: Claudio Gamboa; Phone Number: 415-353-4379; Email: claudio.gamboa@ucsf.edu
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Emory University School of Medicine
      • Contact: Nazanin Soleimanmanesh; Phone Number: 404-251-2599; Email: nazanin.soleimanmanesh@emory.edu
      • Principal Investigator: Marcos Schechter
      • Principal Investigator: Maya Fayfman
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Jessica Gilman; Phone Number: 617-632-8429; Email: jgilman@bidmc.harvard.edu
      • Principal Investigator: Aristidis Veves, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Kourtney Noll; Phone Number: 734-763-0177; Email: kneibaue@med.umich.edu
      • Principal Investigator: Crystal Holmes, DPM
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health
      • Principal Investigator: Alisha Oropallo, MD
      • Contact: Amit Rao; Phone Number: 516-233-3671; Email: ARAO3@NORTHWELL.EDU
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15219
      • Recruiting
      • University of Pittsburgh
      • Contact: Shomita Steiner; Phone Number: 463-237-8770; Email: SSTEINER@pitt.edu
      • Principal Investigator: Chanden Sen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with diabetes with at least one open diabetic foot ulcer.

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Age 18 years or older.
3. Clinically diagnosed with diabetes or meeting the American Diabetes Association (ADA) criteria. [ADA Standards of Clinical Care Diabetes Care 2022, Suppl 1]
4. Open foot ulcer, defined as an open wound from malleolus down. This includes post-surgical wounds within this area left open to heal by secondary intention. In case of multiple ulcers, the largest ulcer will be considered the study index DFU.
5. Agreement to adhere to protocol visits and provide all required biospecimens and clinical data.

Exclusion Criteria:

1. Participation in an interventional clinical trial for DFU within 1 month of Visit 1.
2. Currently receiving radiation to target area or chemotherapy.
3. Gangrene in any portion of the foot with the index ulcer.
4. Planned revascularization or under evaluation for revascularization of the index limb for advanced ischemia within next 4 weeks of Week 0.
5. Severe limb ischemia (SVS WIfl Ischemia grade 3).
6. Any concomitant medical or psychiatric condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Diabetic Foot Ulcer; Adult individuals with at least one diabetic foot ulcer who meet inclusion/exclusion criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Healing	Proportion of participants with complete wound healing by week 52, defined as complete wound closure where there is skin re-epithelialization without drainage or dressing requirements at two consecutive study visits 2 weeks apart.	52 Weeks
DFU Infections	Proportion of participants who develop infections of the index DFU among those with no infections at baseline.	52 Weeks
Amputations	Proportion of participants who have an amputation of the limb associated with the index DFU.	52 Weeks
Prediction Performance	Measures of prediction performance (e.g., predictive power, AUC, ROC, Akaike information criterion) of biomarker(s) for each of the clinical outcomes: Wound Healing, DFU Infections, and Amputations described above. Prediction performance is measured by multiple statistical measures to assess ability of the biomarker to predict event risk for each of the three clinical outcomes.	52 Weeks
Biospecimens Count	Proportion of eligible participants providing biospecimens by site, and by type (serum, plasma, wound fluid, wound dressings, wound debridement tissue, urine).	52 Weeks
Biospecimen Quality	Proportion of biospecimens of adequate quality by type.	52 Weeks
Standard of Care Prescription by Site	Proportion of sites that prescribe the most current SOC into usual care, specifically for: (a) offloading; (b) vascular assessment; and (c) debridement.	52 Weeks
Standard of Care Adherence	Proportion of participants who adhere to physician-prescribed SOC therapies for their DFU care.	52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Healing	Time to healing, defined as the time (in weeks) from baseline to complete healing.	Up to 52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in SF-12 Physical Domain Score	Change from baseline to later of Week 52 or Confirmation Visit in: SF-12 physical domain score. SF-12 for physical; Score range from 0-100; Higher scores indicate better physical health.	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in SF-12 Mental Domain Score	Change from baseline to later of Week 52 or Confirmation Visit in: SF-12 mental domain score.; Score range from 0-100; Higher scores indicate better mental health.	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF subscale leisure score.	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF physical health subscale score.	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF dependence/daily life subscale score.	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF negative emotions subscale score.	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF worried about ulcers/feet subscale score	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF bother by ulcer care subscale score.	Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring; Five-point scale: 1=never to 5=all the time; Score is based on sum of all items; Scored 0-100 - higher scores indicate better QOL	52 Weeks
Change from baseline to later of Week 52 or Confirmation Visit in PROMIS Sleep Disturbance	Change from baseline to later of Week 52 or Confirmation Visit in: PROMIS Sleep disturbance.; Each items has a 5-point response scale; 1=never, 2=rarely, 3=sometimes, 4=often, 5=always; Score ranges from 8-40; higher scores indicate greater severity of sleep disturbance.	52 Weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2028

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: diabetic foot ulcer; Diabetic Foot Consortium
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Diabetes Mellitus; Diabetic Foot
• Other Study ID Numbers: HUM00231478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No