Rapid Pathogen Identification for Diabetic Foot Ulcers

Recruiting in Palo Alto (17 mi)

Overseen by Brian Schmidt, DPM

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Michigan

Disqualifiers: Pregnant, Lactating, Uncontrolled blood glucose, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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).

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 data supports the effectiveness of the treatment using mNGS technology for identifying pathogens in diabetic foot ulcers?

Research shows that metagenomic next-generation sequencing (mNGS) is more sensitive than traditional culture methods, detecting a wider range of pathogens in infections, including diabetic foot ulcers. This technology can identify entire bacterial genomes and antibiotic resistance genes, providing a more complete picture of the infection. ^{1 2 3 4 5}

Is metagenomic next-generation sequencing (mNGS) safe for humans?

The research does not provide specific safety data for metagenomic next-generation sequencing (mNGS) in humans, but it is used as a diagnostic tool to identify pathogens in various infections, suggesting it is generally considered safe for this purpose. ^{4 6 7 8 9}

How does the Rapid Pathogen Identification treatment for diabetic foot ulcers differ from other treatments?

This treatment uses metagenomic next-generation sequencing (mNGS) technology, which is unique because it can identify a wide range of microorganisms and their antibiotic resistance genes in diabetic foot ulcers more accurately than traditional culture methods. This approach provides a comprehensive profile of the microbial community, potentially leading to more effective and targeted treatments. ^{1 10 11 12 13}

Research Team

Brian Schmidt, DPM

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

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

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.

Trial Timeline

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)

Treatment Details

Interventions

• Conventional bacterial culture (Diagnostic Test)
• Rapid diagnostic group using mNGS technology (Device)

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.

Participant Groups

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+

Marschall S. Runge

University of Michigan

Chief Executive Officer since 2015

MD, PhD

Karen McConnell

University of Michigan

Chief Medical Officer since 2020

MD

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Diagnostic Value and Clinical Application of Metagenomic Next-Generation Sequencing for Infections in Critically Ill Patients. [2023]

3. China 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]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Optimizing culture methods according to preoperative mNGS results can improve joint infection diagnosis. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Metagenomic next-generation sequencing for pulmonary infections diagnosis in patients with diabetes. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The Role of Metagenomics and Next-Generation Sequencing in Infectious Disease Diagnosis. [2022]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Clinical assessment of the utility of metagenomic next-generation sequencing in pediatric patients of hematology department. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

The potential of metagenomic next-generation sequencing in diagnosis of spinal infection: a retrospective study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Can molecular DNA-based techniques unravel the truth about diabetic foot infections? [2017]

11. India 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. [2022]

12. England pubmed.ncbi.nlm.nih.gov

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

Bacterial Diversity of Diabetic Foot Ulcers: Current Status and Future Prospectives. [2020]