Continuous Diffusion of Oxygen (CDO) Treatment for Healing of Diabetic Foot Ulcers

Study Overview
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Brief Summary
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This is a pilot study. Maximum 30 subjects with a diabetic foot ulcer (DFU) or surgical foot wound will be consented in order to have 20 eligible subjects who will be enrolled and completed the study. Study duration will be three weeks. Patients will be consented and undergo debridement as standard of care at day 0. Ankle-Brachial Index (ABI), Monofilament Sensory Test and Vibration Perception Threshold(VPT) test will be performed only at day 0. Tissue samples will be taken at this visit during standard of care wound debridement and these tissue samples of the wound would normally be removed as part of routine debridement. These tissue samples of the wound will be used for gene expression and bacterial analysis(research). The patient will then receive topical oxygen therapy using the Transcutaneous O2 device (research) with moist wound dressings for 21 days. Moist wound dressings are used as standard of care. Treatment will be initiated during Screening/Baseline visit(day 0) after routine wound debridement, and patient will receive instructions for home use of the device. The patient will be seen for routine wound debridement at days 7, 14, and 21 with a study window of 5 days., Digital photos of the wound, and vascular evaluations (Transcutaneous oxygen measurements and Hyperspectral imaging. will be performed at each study visit(research). Tissue samples will be taken during standard of care wound debridement at every study visit. Results of the data analysis from this project will be used to inform the design of a larger randomized clinical trial.

Detailed Description
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Patients seen at the University of Texas (UT) Southwestern Wound Clinic with a diabetic foot wound will be identified, consented, and screened for the study. Upon signing consent, patients will be assigned a unique screening number. The screening number given to the first patient will be 01 and increasing sequentially with each subject screened. Screened subjects will be entered onto a screening log. Once a number is assigned it cannot be re-assigned to another subject. At Day 0, a vascular evaluation including ABI, Sensilase, Transcutaneous oxygen measurements, and hyperspectral imaging will be performed. Monofilament Sensory Test and Vibration Perception Threshold(VPT) test will also be performed at day 0.Patients will undergo standard of care wound debridement. Tissue samples will be taken routinely as standard of care. A wound assessment will be performed, including the debridement as standard of care, wound measurements, and digital photos. Gene expression and bacterial analysis will be performed on tissue samples. After tests are performed, patient will receive topical oxygen therapy using the Transcutaneous O2 device with moist wound dressings. Moist wound dressings are used as standard of care. Patient will receive instructions to continue treatment at home. Patient will return for an appointment at days 7, 14, and 21, where vascular assessment (Sensilase, Transcutaneous oxygen measurements, Hyperspectral imaging) ,wound assessment (wound measurements, digital photos and acetate tracings) and tissue sampling will be performed following standard of care debridement, Patient will cease topical oxygen treatment at day 21, and study will be concluded.

Official Title
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Continuous Diffusion of Oxygen (CDO) Treatment for Healing of Diabetic Foot Ulcers

Conditions
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Foot Ulcer, Diabetic

Intervention / Treatment
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* Device: Transcutaneous O2 device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects of all races and ethnicities, age 18-89 Diagnosis of diabetes mellitus Has a diabetic foot ulcer Exclusion Criteria: End-stage renal disease (ESRD) Has untreated foot ulcer at time of study HIV, hepatitis, autoimmune disease, Systemic lupus erythematous (SLE), Raynaud's disease Ankle-Brachial Index (ABI) < 0.4 Unable or unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous O2 device<br>Continuous diffusion of oxygen (CDO) (topical oxygen) therapy, which will be administered using a portable device. | Device: Transcutaneous O2 device<br>* A portable device that delivers continuous diffusion of oxygen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue Oxygenation as Measured by Hyperspectral Imaging | Hyperspectral (HyperMed, Inc.) images were taken for evaluation of tissue oxygenation following debridement at Visit 1 (day 0), visit 2 (day 7), visit 3 (day 14), visit 4 (day 21). Two images were taken of the study foot - one of the plantar surface and one of the dorsal surface to evaluate the oxygenation of the entire foot. Measurements of oxygenated hemoglobin are generated by the camera for each image. Results are reported in aggregate as mean/standard error for all time points. | 21 days | 
| Tissue Perfusion as Measured by TCPO2 | Transcutaneous oxygen pressure (TCPO2) was measured at visit 1 (day 0), visit 2 (day 7), visit 3 (day 14), visit 4 (day 21) to assess perfusion of the tissue. This is measured at the medial and lateral foot to include both major blood vessels to the foot. Reported here as aggregate mean over all time points. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | Comparison of measurements inflammatory cytokines: Interleukin 6 (IL-6), Interleukin 8 (IL-8), tumor necrosis factor (TNF)-α and growth factors: vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), insulin derived growth factor (IGF), transforming growth factor beta (TGF)-β. These are reported as log fold change by delta delta ct. Evaluated from tissue samples obtained at visit 1 (day 0), visit 2 (day 7), visit 3 (day 14), visit 4 (day 21). | 21 days | 
| Evaluate Changes in Bacterial Infection | Tissue samples sent for 16s rRNA quantitative culture. Reported in aggregate for each visit that corresponds to Visit 1 (day 0), visit 2 (day 7), visit 3 (day 14), visit 4 (day 21). | 21 days | 
| Percent Wound Area Reduction | Percent change of the wound area (measured in cm^2) of visit 2 (day 7), visit 3 (day 14), and visit 4 (day 21) compared to baseline. Percent area reduction = initial surface area (length in cm x width in cm) minus current surface area (length in cm x width in cm), divided by initial surface area. multiplied by 100 to get percentage. | 21 days |