Diabetic Foot Ulcer (DFU) Rapid Pathogen Identification

The Role of the Microbiome in Diabetic Foot Ulcers

The purpose of this study is to evaluate the role of rapid diagnosis of pathogens in treatment of infection and wound healing in diabetic foot ulcers. This research is studying the use of a new device of people to learn if metagenomic next generation sequencing (mNGS) techniques technology is a feasible tool that can be used to direct targeted antibiotic therapy in infected diabetic foot ulcers.

Participant's tissue will be randomized to usual care tissue collection and cultures (standard of care) or usual care tissue collection and cultures (standard of care) plus metagenomics next generation sequencing (mNGS). The participant's will not be randomized to any treatment (i.e. antibiotic therapy).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetic Foot Ulcer; Wound
• Intervention / Treatment: Diagnostic test: Conventional bacterial culture; Device: Rapid diagnostic group using mNGS technology

Detailed Description

Participants will have tissue taken per standard of care at the baseline visit. In addition, participants will complete of a comprehensive medical history questionnaire, Michigan Neuropathy questionnaires, and have assessments of the foot ulcer or wound. The study team will follow participants for approximately 12 weeks.

Initial antibiotic therapy to treat diabetic foot ulcer infections are determined by participants treating provider and are based on clinical characteristics, drug allergies or sensitivities, and suspected causative pathogen (i.e., bacteria). In this study, the identification of pathogens using mNGS will be given to the treating physician and may result in additional or different antibiotics.

The decision for antibiotic prescription(s) to treat the diabetic foot ulcer infection will be made by treating providers. The antibiotic plan will be updated according to final culture results (usually 4-6 days following culture of tissue). For those participants randomized to the mNGS cohort, the results (usually 24-36 hours following culture of tissue) will be shared with the treating physician. The treating physician may provide additional or different treatment than initially prescribed.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with diabetes mellitus

• Have an infected DFU with a surface area ≥0.5 square centimeter (cm2)

  o DFU Infection status will be clinically recorded at time of enrollment according to Infectious Disease Society of America (IDSA): mild, moderate, or severe infection

• Have a hemoglobin A1c[HbA1c] of 12% or less as measured within the last 6 months,
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• Pregnant or lactating
• Uncontrolled blood glucose as demonstrated by a HbA1c of greater than 12%
• Bilateral wound or ulcer
• Current infection of Coronavirus disease 2019 (COVID19)
• Unable to provide informed consent or are unwilling to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional bacterial culture; Wound tissue removed will be sent for standard of care evaluation.	Diagnostic test: Conventional bacterial culture; Participants will have DFU ulcer tissue collected and sent to the laboratory (per usual care practices) that includes the use of conventional bacterial culture analysis (i.e., plates).
Experimental: Conventional bacterial culture plus rapid diagnostic group; Wound tissue removed will be sent for standard of care evaluation as well as rapid diagnostic with metagenomics next generation sequencing (mNGS).	Diagnostic test: Conventional bacterial culture; Participants will have DFU ulcer tissue collected and sent to the laboratory (per usual care practices) that includes the use of conventional bacterial culture analysis (i.e., plates).; Device: Rapid diagnostic group using mNGS technology; Participants will have DFU ulcer tissue collected and have metagenomics sequencing performed. The name of the devices listed for this study are the Illumina MiSeq System with MiSeq Reagent Kit V2 from Illumina and the MinION sequencer (Oxford Nanopore Technologies).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percent change in foot ulcer surface area square centimeter (cm2) after 12 weeks of observation for infected diabetic foot ulcers	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of participants with an infected DFU at baseline that resolve clinical infection by study week 4		Baseline to 4 weeks
Percent of clinical resolved infected DFU for infected DFU participants with clinically resolved infection defined as improvement of greater or equal to two clinical signs of infection	Clinical signs of infection includes: local swelling or induration, erythema, local tenderness or pain, local warmth, purulent discharge) with no requirement for additional antibiotics upon follow-up appointments.	Baseline up to 12 weeks
Total days of antibiotic therapy for the infected DFU participants		Baseline up to 12 weeks
Number of days to infection resolution for the infected DFU participants		Baseline up to 12 weeks
The percentage of participants with an infected DFU at baseline that undergo a non-traumatic lower extremity amputation during the study.		Baseline up to 12 weeks
The percentage of participants with an infected DFU at baseline that are hospitalized for infection during the study.		Baseline up to 12 weeks
Post study percentage change of wound surface area (cm2).		Baseline up to 12 weeks
Proportion of participants that reach a 50% reduction in surface area (cm2) of the infected DFU		Baseline up to 12 weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Brian Schmidt, DPM, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2024
• Primary Completion (Actual): February 18, 2026
• Study Completion (Actual): February 18, 2026

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Next generation sequencing; Wound Infection; Wound assessments; Wound's microbiome
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Infections; 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; Wounds and Injuries; Diabetes Mellitus; Diabetic Foot; Wound Infection
• Other Study ID Numbers: HUM00251960; K23DK131261 (U.S. NIH Grant/Contract)

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: Yes
• product manufactured in and exported from the U.S.: No