Use of Real-time Fluorescence Imaging in Diabetic Foot Ulcers: the Impact of Colonization

Study Overview
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Brief Summary
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The study evaluates the efficacy of fluorescence-guided de-colonization in patients with non-infected diabetic foot ulcers. The efficacy will also be compared between those who used artificial dermis and split-thickness skin graft for reconstruction surgery.

Detailed Description
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Diabetic foot ulcers (DFU) are the main cause of hospitalization in diabetic patients. These hard-to-heal ulcers have a high amputation rate, and a 5-year mortality rate of 50% once being amputated. Treatments for DFU include infection management, wound debridement, revascularization, pressure off-loading, etc. Recently, a novel imaging device called MolecuLight i:X was introduced to help visualize clinically undetectable fluorescent bacteria in wounds and has shown promising effects in the identification of infection. However, as microorganisms almost colonize all chronic wounds, the term bacterial colonization should be distinguished from clinical infection. While infection delays the healing process, the impact of colonization on wound reconstruction remains unclear; and the assessment is often more difficult on DFU patients with peripheral neuropathy and vascular diseases. In the present study, investigators will conduct a prospective randomized controlled trial to evaluate the clinical outcome of achieving high-quality de-colonization with the aid of MolecuLight i:X in the treatment of noninfected DFU patients, and to compare its efficacy between artificial dermis and split-thickness skin graft.

Official Title
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Use of Real-time Fluorescence Imaging in Diabetic Foot Ulcers: A New Strategy to Assess Residual Bacterial Colonization Before Application of Artificial Dermis or Split-thickness Skin Graft

Conditions
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Infection, Surgical Site

Intervention / Treatment
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* Device: MolecuLight


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 ≤ age < 80 Body mass index (BMI) < 35 kg/m2 Glycated hemoglobin (HbA1c) < 10% Target ulcer: (1) 10 ≤ size < 100 cm2 (2)Located on or below malleolus (3)Wagner's grade 2 or 3 initially (4)Margin > 3 cm between target ulcer and other ulcers Transcutaneous oxygen pressure (TcPO2) ≥ 30 mmHg and 0.8 ≤ ankle-brachial index (ABI) ≤ 1.2 Patient willingness and signed informed consent Exclusion Criteria: Pregnancy Type I diabetes mellitus (Type I DM) Active malignancy Taking glucocorticoids, immunosuppressants, or in an immunocompromised status Lab test upon admission for reconstruction surgery: (1) hemoglobin (Hb) < 8.0 g/dL, or white blood cell (WBC) < 3000 cell/μg (2) aspartate aminotransferase (AST) / alanine aminotransferase (ALT) / total bilirubin > 3x upper normal limits (3) albumin < 2.5 g/dL

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluorescence-guided<br>Patients who used MolecuLight to achieve high-quality de-colonization during reconstruction surgery with artificial dermis or split-thickness skin graft | Device: MolecuLight<br>* MolecuLight is a handheld fluorescence imaging device that is utilized to help real-time visualize clinically undetectable fluorescent bacteria in wounds. It emits a 405 nm wavelength of safe violet light, which interacts with the wound tissue and bacteria causing certain bacteria to emit red or cyan fluorescence. The fluorescence signals were then captured by MolecuLight and those with bacteria at levels of ≥ 10^4 colony forming units per gram (CFU/g) will be detected and displayed on the screen.<br>|
| No Intervention: Control<br>Patients who did not use MolecuLight to achieve high-quality de-colonization during reconstruction surgery with artificial dermis or split-thickness skin graft | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete healing time | The time for complete wound epithelialization or closure without drainage after reconstruction surgery. | 180 days after reconstruction surgery | 
| Wound healing rate on 30, 60, 90 and 180 days | The healing percentage of wound 30, 60, 90 and 180 days after reconstruction surgery. | 180 days after reconstruction surgery | 
| Artificial dermis (AD) or split-thickness skin graft (STSG) take rate | The take percentage of artificial dermis or split-thickness skin graft 21 days after reconstruction surgery. | 21 days after reconstruction surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of bacteria before MolecuLight de-colonization | The percentage of bacteria after the last debridement without using MolecuLight to do de-colonization. | Immediately after last debridement | 
| Percentage of bacteria after MolecuLight de-colonization | The percentage of bacteria after using MolecuLight to do de-colonization. | Immediately after de-colonization with MolecuLight | 
| Wound surface area on 30, 60, 90 and 180 days | The surface area of wound 30, 60, 90 and 180 days after reconstruction surgery. | 30, 60, 90 and 180 days after reconstruction surgery | 
| Reasons for poor AD or STSG take rate | Reasons for poor take rate of artificial dermis or split-thickness skin graft 21 days after reconstruction surgery may include as follows: (1) weak graft fixation (2) seroma (3) hematoma (4) wound localized infection (5) osteomyelitis (6) irreversible ischemic ulcers (7) systemic cause | 21 days after reconstruction surgery | 
| Complications on 180 days | Complications evaluated 180 days after reconstruction surgery may include as follows: (1) wound recurrence (2) higher-level amputation (3) above or below knee amputation (4) vascular restenosis (5) mortality | 180 days after reconstruction surgery | 
| Vancouver scar score on 180 days | The vancouver scar score of wound evaluated 180 days after reconstruction surgery. | 180 days after reconstruction surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MolecuLight, diabetic foot ulcer, non-infected, autofluorescence, fluorescence imaging, artificial dermis, split thickness skin graft