Clinical trial NCT05172089: Diabetic Foot Ulcer (DFU) Biofilm Infection and Recurrence
Official title: Diabetic Foot Ulcer (DFU) Biofilm Infection and Recurrence
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Wounds
Biofilm Infection
Trans-epidermal Water Loss (TEWL)
Diabetic Foot
Diabetic Foot Infection
Keywords: foot ulcer
diabetic foot
wound infection
diabetic foot ulcer
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: University of Arizona
First posted: 2021-12-29
Enrollment: 405
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: clinically diagnosed Diabetic Foot Ulcer (DFU) patients who are suspected to be infected will be recruited for this larger cohort of patients in the parent study.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Biofilm infection abundance
timeFrame: 16 weeks
measure: TEWL
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Cranberry Township
country: United States
facility: UPMC Wound Healing Services at UPMC Passavant
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Chandan K Sen, PhD
role: PRINCIPAL_INVESTIGATOR
References: