Diabetic Foot Ulcer (DFU) Biofilm Infection and Recurrence (DFUBiofilm)

University of Pittsburgh

Status: Enrolling

Conditions: Trans-epidermal Water Loss (TEWL); Diabetic Foot; Chronic Wounds; Diabetic Foot Infection; Biofilm Infection

Treatments: Procedure: Observation of wound infection and time to wound closure; Device: Pericam PSI-NR Laser Speckle imaging

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05172089

STUDY23050116

3R01DK125835-02S1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This work is based on DFU patients, seeks to conduct a fully powered clinical study testing i) If DFU with a history of biofilm infection closes with deficient barrier function. ii) whether such functionally deficient wound closure, manifested as high TEWL, is associated with greater wound recurrence. The primary parent study will also address molecular mechanisms implicated in biofilm-induced loss of skin epithelial barrier integrity in DFU patients.

Full description

Diabetic foot ulcers (DFU) are one of the most common reasons for hospitalization of diabetic patients and frequently results in amputation of lower limbs. Of the one million people who undergo non-traumatic leg amputations annually worldwide, 75% are performed on people who have type 2 diabetes (T2DM). The risk of death at 10 years for a diabetic with DFU is twice as high as the risk for a patient without a DFU. The rate of amputation in patients with DFU is 38.4%4. Infection is a common (>50%) complication of DFU. Emerging evidence underscores the significant risk that biofilm infection poses to the non-healing DFU. Biofilms are estimated to account for 60% of chronic wound infections. In the biofilm form, bacteria are in a dormant metabolic state. Thus, standard clinical techniques like the colony forming unit (CFU) assay to detect infection may not detect biofilm infection. Thus, biofilm infection may be viewed as a silent maleficent threat in wound care.

n the current standard of care (SoC), wound closure is defined (FDA) by wound area re-epithelialization without drainage. The investigators' pre-clinical large animal work demonstrates that wounds with a history of biofilm infection may meet above criteria, but the repaired wound-site skin is deficient in barrier function. This has led to the concept of functional wound closure wherein the current clinical definition of wound closure is supplemented with a functional parameter - restoration of skin barrier function as measured by low trans-epidermal water loss (TEWL).

This study rests pilot study showing that closed DFU with deficient barrier function are more likely to recur. Biofilm infection as assessed through scanning electron microscopy and wheat germ agglutin assay performed on debrided tissue causes faulty re-epithelialization, compromising skin barrier function at the closed wound site. This work is based on DFU patients, seeks to conduct a fully powered clinical study testing i) If DFU with a history of biofilm infection closes with deficient barrier function. ii) whether such functionally deficient wound closure, manifested as high TEWL, is associated with greater wound recurrence. The primary parent study will also address molecular mechanisms implicated in biofilm-induced loss of skin epithelial barrier integrity in DFU patients.

Enrollment: 405 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or Female, Age ≥ 18
• Willing to comply with protocol instructions, including all study visits and study activities.
• Patient with an open Diabetic Foot Ulcer
• Adequate arterial blood flow as evidenced by at least one of the following (for wounds below the knee):
• TcOM >30 mmHg
• Ankle-brachial index ≥0.7-1.20
• Toe pressure > 30 mmHg
• TBI > 0.6 mmHg

Exclusion criteria

• Individuals who are deemed unable to understand the procedures, risks, and benefits of the study.
• Wounds closed or to be surgically closed by flap or graft coverage
• Subjects with marked immunodeficiency (HIV/AIDS, or on immunosuppressive medications.
• TcOM < 30mmHg
• Diabetics with a hemoglobin A1c > 12 within 3 months prior to enrollment
• Subject with autoimmune connective tissue disease
• Ulcer size and location that does not allow the TEWL measurement per SOP
• Pregnant women
• Prisoners
• Unable to comply with study procedures and/or complete study visits

Trial design

405 participants in 1 patient group

Diabetic Foot Ulcer study

Description:

405 clinically diagnosed Diabetic Foot Ulcer (DFU) patients who are suspected to be infected will be recruited . Wound swab for culture obtained. Baseline digital imaging of target wound(s). SF-12 Health survey, Visual Analogue Pain scale, Cardiff wound impact questionnaires. Wound site evaluation including TcOM/TBI/ankle brachial index (ABI) will be completed for subjects with wounds below the knee, if not already completed per standard of care within the previous 12 months. Hemoglobin A1c point of care testing will be drawn for diabetic subjects who do not have an A1c available within 90 days prior to enrollment; 3mm biopsy tissue or debrided tissue will be collected. Ideally, two tissue samples will be obtained; the subject's medical records will be reviewed and followed for up to 16 weeks or until their wound has closed, whichever comes first. The research staff will also call the patient or care facility as needed to check for wound closure.