Rapid Pathogen Identification for Diabetic Foot Ulcers

Overseen By Brian M Schmidt, DPM

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Pregnant, Lactating, Uncontrolled blood glucose, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to quickly identify germs in infected diabetic foot ulcers. The aim is to determine if metagenomic next-generation sequencing (mNGS) can help doctors select the best antibiotics more quickly, potentially improving wound healing. Participants will have their wound tissue tested using conventional bacterial culture or both conventional methods and the new mNGS approach. The study seeks individuals with diabetes who have an infected foot ulcer at least 0.5 square centimeters in size. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance future treatment options for diabetic foot ulcers.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems focused on testing a new diagnostic tool rather than changing your treatment.

What prior data suggests that this device is safe for use in diagnosing diabetic foot ulcers?

Research has shown that metagenomic next-generation sequencing (mNGS) is a promising method for identifying bacteria in diabetic foot ulcers. However, specific safety information for mNGS itself is not available. Researchers use this method alongside regular culture techniques to better understand infections. It is important to note that mNGS is a diagnostic tool, not a treatment, and does not involve taking medication or undergoing invasive procedures.

Since the study does not involve a new drug or invasive treatment, the risks are likely low. The focus is on gathering information from the wound to guide treatment. For those considering participation, the study aims to enhance understanding of infections to improve treatment effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a cutting-edge method called metagenomics next generation sequencing (mNGS) to rapidly identify pathogens in diabetic foot ulcers. Unlike conventional bacterial cultures, which can take days to yield results, mNGS has the potential to quickly detect a wide range of bacteria, viruses, and fungi from a single sample. This speed and comprehensiveness could lead to faster and more accurate treatment decisions, improving patient outcomes and reducing the risk of complications. By enabling healthcare providers to tailor treatments more precisely, this innovative approach might revolutionize how diabetic foot infections are managed.

What evidence suggests that this trial's diagnostic methods could be effective for diabetic foot ulcers?

Research shows that metagenomic next-generation sequencing (mNGS) can identify bacteria in diabetic foot ulcers. In this trial, one group of participants will receive the conventional bacterial culture, while another group will receive both the conventional bacterial culture and the rapid diagnostic using mNGS technology. Studies have found that mNGS detects more types of bacteria than traditional methods. This allows doctors to identify and treat the right bacteria more effectively, potentially speeding up infection healing. Past research demonstrated that mNGS helps identify specific germs in these wounds, crucial for selecting the best antibiotics. Early results suggest that using mNGS may lead to better infection control and improved healing in diabetic foot ulcers. ^{1 2 3 4 5}

Who Is on the Research Team?

Brian Schmidt, DPM

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with diabetic foot ulcers. Participants should have an infection in their ulcer and be willing to undergo tissue collection. The study excludes those who cannot give informed consent, are pregnant or breastfeeding, or have conditions that may interfere with the study.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

My foot ulcer is infected and larger than 0.5 square cm.

I have diabetes.

Exclusion Criteria

Pregnant or lactating

Uncontrolled blood glucose as demonstrated by a HbA1c of greater than 12%

I have wounds or ulcers on both sides of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants will have tissue taken per standard of care and complete medical history and neuropathy questionnaires

1 visit

1 visit (in-person)

Treatment

Participants receive standard of care or standard of care plus mNGS for pathogen identification to guide antibiotic therapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up appointments to assess clinical resolution of infection

12 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Conventional bacterial culture
• Rapid diagnostic group using mNGS technology

Trial Overview The trial is testing if rapid pathogen identification using metagenomic next generation sequencing (mNGS) can help in treating infections and healing wounds in diabetic foot ulcers compared to conventional bacterial culture methods.

How Is the Trial Designed?

Group I: Conventional bacterial culture plus rapid diagnostic group Experimental Treatment 2 Interventions

Wound tissue removed will be sent for standard of care evaluation as well as rapid diagnostic with metagenomics next generation sequencing (mNGS).

Group II: Conventional bacterial culture Active Control 1 Intervention

Wound tissue removed will be sent for standard of care evaluation.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Metagenomic next-generation sequencing (mNGS) significantly enhances the identification of infectious agents in joint infections compared to conventional culture methods, providing more detailed aetiological information.

By optimizing culture methods based on mNGS results, the sensitivity of intraoperative microbial cultures improved to 94.29%, compared to only 60% with standard culture techniques, indicating a substantial increase in diagnostic efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing culture methods according to preoperative mNGS results can improve joint infection diagnosis. Fang, X., Cai, Y., Mei, J., et al.[2021]

Metagenomic next-generation sequencing (mNGS) demonstrated high sensitivity (96.6%) and good specificity (83.1%) for detecting bacterial and fungal infections in a study of 234 critically ill patients, indicating its effectiveness compared to conventional microbiological testing.

mNGS-guided treatment adjustments were more beneficial for immunocompromised patients (48.5%) than for immunocompetent patients (30.1%), suggesting that mNGS can enhance precision medicine in managing infections, especially in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Value and Clinical Application of Metagenomic Next-Generation Sequencing for Infections in Critically Ill Patients. He, Y., Geng, S., Mei, Q., et al.[2023]

The metagenomic next-generation sequencing (mNGS) method detected significantly more pathogens (75) compared to the traditional microbial culture method (35) in a study of 23 specimens from 11 patients with burns and wounds, indicating its higher sensitivity.

mNGS not only identified a greater variety of pathogens, including bacteria, fungi, and viruses, but also provided insights into the relative abundance of these pathogens, making it a valuable tool for diagnosing infections in burn and wound patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of metagenomic next-generation sequencing technology in pathogen detection in patients with burns and patients with acute or chronic wounds]. Li, F., Yin, KN., Hu, Q., et al.[2021]

In a study of 184 hospitalized patients with pulmonary infections, metagenomic next-generation sequencing (mNGS) demonstrated a significantly higher microbial detection rate in diabetic patients (95.3%) compared to conventional testing (67.4%), particularly for bacterial infections.

mNGS proved to be a valuable diagnostic tool for identifying pathogens in diabetic patients, successfully detecting bacteria in 92.9% of cases that conventional tests missed, highlighting its efficacy in managing pulmonary infections in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metagenomic next-generation sequencing for pulmonary infections diagnosis in patients with diabetes. Zhang, S., Ou, J., Tan, Y., et al.[2023]

Metagenomic next-generation sequencing (mNGS) is a powerful tool for pathogen detection, showing sensitivity comparable to specific PCR assays and the ability to identify a wider range of potential pathogens than traditional methods.

Despite its advantages, mNGS raises concerns about contamination and the detection of nonclinically significant organisms, highlighting the need for careful interpretation of results and further studies to assess its impact on clinical outcomes and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Metagenomics and Next-Generation Sequencing in Infectious Disease Diagnosis. Miller, S., Chiu, C.[2022]

In a study of 70 febrile inpatients suspected of having infections, Metagenomic Next-Generation Sequencing (mNGS) significantly improved pathogen detection, identifying possible pathogens in cases where traditional tests failed, leading to antibiotic adjustments in 78.6% of patients.

mNGS not only helped in confirming infections but also played a crucial role in ruling out unnecessary treatments, thereby enhancing clinical management and potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical assessment of the utility of metagenomic next-generation sequencing in pediatric patients of hematology department. Shen, H., Shen, D., Song, H., et al.[2021]

Metagenomic next-generation sequencing (mNGS) demonstrated a sensitivity of 70.3% in identifying pathogens in spinal infections, which is significantly higher than the 14.8% sensitivity of traditional culture methods, indicating mNGS's potential as a more effective diagnostic tool.

The specificity of mNGS was found to be 75.0%, which is comparable to that of culture tests, suggesting that while mNGS is more sensitive, both methods have similar accuracy in confirming infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of metagenomic next-generation sequencing in diagnosis of spinal infection: a retrospective study. Ma, C., Wu, H., Chen, G., et al.[2022]

Molecular techniques like metagenomics and shotgun sequencing can reveal a much greater diversity of microorganisms in diabetic foot infections compared to traditional culture methods, which often miss many species.

These advanced methods not only identify which microorganisms are present but also provide insights into their potential functions, such as virulence and pathogenicity, which could lead to better-targeted treatments and improved clinical outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can molecular DNA-based techniques unravel the truth about diabetic foot infections? Malone, M., Gosbell, IB., Dickson, HG., et al.[2017]

In a study of 65 diabetic patients with foot ulcers, Pseudomonas aeruginosa was identified as the most common pathogen, found in 23.3% of cases, highlighting the need for targeted antibiotic therapy based on local bacterial prevalence.

Burkholderia cepacia, previously uncommon in diabetic foot ulcers, was found in 10% of cases, suggesting a shift in infection patterns possibly due to environmental changes and inadequate waste management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinico-Microbiological Profile and Culture Sensitivity Pattern of Micro-Organisms Isolated from Diabetic Foot Ulcers: Study from a Tertiary Care Centre. ShankarRao, AG., Behera, PK., Tripathy, KP., et al.[2022]

Infected leg ulcers in diabetic patients are often polymicrobial, meaning they can be caused by multiple types of bacteria, including aerobic Gram-negative bacilli, anaerobes, and Staphylococcus aureus, making accurate identification of pathogens crucial for effective treatment.

Curettage and deep tissue cultures are the best methods for identifying these pathogens, allowing for targeted antibiotic therapy that can prevent the unnecessary long-term use of broad-spectrum antibiotics and reduce complications from foot infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of the diabetic foot ulcer. Gentry, LO.[2019]

Diabetic foot ulcers (DFUs) and infections (DFIs) significantly impact patient quality of life and can lead to serious complications like amputations and high mortality rates.

Advancements in DNA and RNA technologies, such as metagenomics and metatranscriptomics, provide more accurate bacterial identification in DFUs/DFIs compared to traditional culture methods, potentially leading to improved treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial Diversity of Diabetic Foot Ulcers: Current Status and Future Prospectives. Sadeghpour Heravi, F., Zakrzewski, M., Vickery, K., et al.[2020]

Clinical metagenomic next-generation sequencing (mNGS) offers a comprehensive and rapid diagnostic tool for identifying a wide range of pathogens, including viruses, bacteria, fungi, and parasites, which traditional methods like PCR may not cover.

Despite its potential for quick diagnosis of infectious diseases, the implementation of mNGS in clinical settings faces challenges, including the need for standardized guidelines and best practices to ensure accurate interpretation of results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical application of metagenomic next-generation sequencing for detecting pathogens in bronchoalveolar lavage fluid: case reports and literature review. Tsang, HF., Yu, ACS., Jin, N., et al.[2022]

Next-generation sequencing (NGS) identified a greater diversity of pathogens in infected diabetic foot ulcers (DFUs) compared to standard culture methods, revealing an average of 5.1 pathogens per sample versus 2.6 from culture.

NGS demonstrated a 70% concordance rate with standard culture in identifying pathogens, but it also provided insights into antibiotic resistance genes, highlighting its potential as a more comprehensive diagnostic tool for managing orthopedic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers. Choi, Y., Oda, E., Waldman, O., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11758752/

mNGS for Diabetic Foot Ulcer Microbial Characteristics Application of metagenomic next-generation sequencing (mNGS) to describe the microbial characteristics of diabetic foot ulcers at a tertiary ...

2. bmcendocrdisord.biomedcentral.com bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-025-01837-z

Metagenomic Sequencing of Diabetic Foot Ulcers In this study, we utilized a routine culture method and mNGS to analyze the same DFU wound samples and the results were compared.

3. withpower.com withpower.com/trial/phase-diabetic-foot-ulcers-dfus-8-2024-a5d91

Rapid Pathogen Identification for 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.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39849445/

Diabetic Foot Ulcer Microbial Characteristics: mNGS Application of metagenomic next-generation sequencing (mNGS) to describe the microbial characteristics of diabetic foot ulcers at a tertiary medical center in South China. BMC Endocr Disord. 2025 Jan 24;25(1):18. doi: 10.1186/s12902-025-01837-z.

5. researchgate.net researchgate.net/publication/388355998_Application_of_metagenomic_next-generation_sequencing_mNGS_to_describe_the_microbial_characteristics_of_diabetic_foot_ulcers_at_a_tertiary_medical_center_in_South_China

Application of metagenomic next-generation sequencing ... Metagenomic next-generation sequencing (mNGS) has been a useful supplement to routine culture method for the etiological diagnosis of DFUs. In ...