Diabetes Mellitus, Diabetic Foot Ulcer, Wound
Conditions
Keywords
Wound Infection, Wound assessments, Wound's microbiome, Next generation sequencing
Brief summary
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).
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.
Interventions
DIAGNOSTIC_TESTConventional 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).
DEVICERapid 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).
Sponsors
University of Michigan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants will be randomized 1:1 to the control and intervention arms using block randomization. Only tissue review will be randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline up to 12 weeks | 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. |
| 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 resolve clinical infection by study week 4 | Baseline to 4 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 | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrian Schmidt, DPM
University of Michigan
Outcome results
None listed