Foot Ulcer, Diabetic
Conditions
Brief summary
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
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.
Interventions
DEVICETranscutaneous O2 device
A portable device that delivers continuous diffusion of oxygen.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tissue Oxygenation as Measured by Hyperspectral Imaging | 21 days | 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. |
| Tissue Perfusion as Measured by TCPO2 | 21 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | 21 days | 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). |
| Evaluate Changes in Bacterial Infection | 21 days | 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). |
| Percent Wound Area Reduction | 21 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcutaneous O2 Device Continuous diffusion of oxygen (CDO) (topical oxygen) therapy, which will be administered using a portable device.
Transcutaneous O2 device: A portable device that delivers continuous diffusion of oxygen. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Transcutaneous O2 Device |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Race/Ethnicity, Customized African American | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 11 Participants |
| Race/Ethnicity, Customized Hispanic | 7 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 2 / 23 |
| serious Total, serious adverse events | 1 / 23 |
Outcome results
Primary
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.
Time frame: 21 days
Population: There was no control arm for this study. For analysis, groups were analyzed as healer and nonhealer. Healers are defined by those patients who achieved a 50% wound area reduction in the study time frame and are likely to heal within 12 weeks. Nonhealers did not reach a 50% wound area reduction in the study time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcutaneous O2 Device | Tissue Oxygenation as Measured by Hyperspectral Imaging | Dorsal oxyhemoglobin - healer | 63.58 percent concentration of oxyhemoglobin | Standard Error 11.17 |
| Transcutaneous O2 Device | Tissue Oxygenation as Measured by Hyperspectral Imaging | Dorsal oxyhemoglobin - nonhealer | 61.91 percent concentration of oxyhemoglobin | Standard Error 9.14 |
| Transcutaneous O2 Device | Tissue Oxygenation as Measured by Hyperspectral Imaging | Plantar oxyhemoglobin - healer | 76.33 percent concentration of oxyhemoglobin | Standard Error 4.86 |
| Transcutaneous O2 Device | Tissue Oxygenation as Measured by Hyperspectral Imaging | Plantar oxyhemoglobin - nonhealer | 77.55 percent concentration of oxyhemoglobin | Standard Error 5.9 |
Primary
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.
Time frame: 21 days
Population: There was no control arm for this study. For analysis, groups were analyzed as healer and nonhealer. Healers are defined by those patients who achieved a 50% wound area reduction in the study time frame and are likely to heal within 12 weeks. Nonhealers did not reach a 50% wound area reduction in the study time frame
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcutaneous O2 Device | Tissue Perfusion as Measured by TCPO2 | Transcutaneous oxygen - medial foot - nonhealer | 53.64 mmHg | Standard Error 3.97 |
| Transcutaneous O2 Device | Tissue Perfusion as Measured by TCPO2 | Transcutaneous oxygen - lateral foot - healer | 55.21 mmHg | Standard Error 3.46 |
| Transcutaneous O2 Device | Tissue Perfusion as Measured by TCPO2 | Transcutaneous oxygen - medial foot - healer | 53.31 mmHg | Standard Error 4.33 |
| Transcutaneous O2 Device | Tissue Perfusion as Measured by TCPO2 | Transcutaneous oxygen - lateral foot - nonhealer | 59.31 mmHg | Standard Error 4.68 |
Secondary
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).
Time frame: 21 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL-6 Visit 2 | 11.37 log fold change | Standard Error 5.11 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | PDGF visit 1 | 1.40 log fold change | Standard Error 0.23 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | PDGF visit 2 | 3.92 log fold change | Standard Error 1.31 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | PDGF visit 3 | 1.76 log fold change | Standard Error 0.37 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL-6 visit 1 | 2.68 log fold change | Standard Error 0.82 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL-6 Visit 3 | 18.24 log fold change | Standard Error 6.48 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL-6 Visit 4 | 9.12 log fold change | Standard Error 2.53 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL8 visit 1 | 3.97 log fold change | Standard Error 1.9 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL8 visit 2 | 3.12 log fold change | Standard Error 1.31 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL8 visit 3 | 7.51 log fold change | Standard Error 2.89 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IL8 visit 4 | 5.22 log fold change | Standard Error 2.38 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TNFa visit 1 | 1.82 log fold change | Standard Error 0.41 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TNFa visit 2 | 8.17 log fold change | Standard Error 2.26 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TNFa visit 3 | 5.03 log fold change | Standard Error 1.73 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TNFa visit 4 | 3.27 log fold change | Standard Error 1.19 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | VEGF visit 1 | 1.37 log fold change | Standard Error 0.26 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | VEGF visit 2 | 5.85 log fold change | Standard Error 1.4 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | VEGF visit 3 | 4.35 log fold change | Standard Error 1.42 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | VEGF visit 4 | 3.29 log fold change | Standard Error 0.99 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | PDGF visit 4 | 1.81 log fold change | Standard Error 0.52 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IGF1 visit 1 | 3.04 log fold change | Standard Error 1.18 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IGF1 visit 2 | 19.91 log fold change | Standard Error 9.1 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IGF1 visit 3 | 5.47 log fold change | Standard Error 2.46 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | IGF1 visit 4 | 5.25 log fold change | Standard Error 2 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TGFb visit 1 | 1.27 log fold change | Standard Error 0.19 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TGFb visit 2 | 10.42 log fold change | Standard Error 3.05 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TGFb visit 3 | 4.65 log fold change | Standard Error 1.22 |
| Transcutaneous O2 Device | Change in Levels of Growth Factors and Cytokines Involved in Wound Healing | TGFb visit 4 | 3.96 log fold change | Standard Error 1.26 |
Secondary
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).
Time frame: 21 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcutaneous O2 Device | Evaluate Changes in Bacterial Infection | Visit 4 | 598557.90 CFU/ml | Standard Deviation 2303848.45 |
| Transcutaneous O2 Device | Evaluate Changes in Bacterial Infection | Visit 1 | 137071.35 CFU/ml | Standard Deviation 204854.93 |
| Transcutaneous O2 Device | Evaluate Changes in Bacterial Infection | Visit 2 | 433719.88 CFU/ml | Standard Deviation 1009663.23 |
| Transcutaneous O2 Device | Evaluate Changes in Bacterial Infection | Visit 3 | 276842.20 CFU/ml | Standard Deviation 603627.08 |
Secondary
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.
Time frame: 21 days
Population: There was no control arm for this study. For analysis, groups were analyzed as healer and nonhealer. Healers are defined by those patients who achieved a 50% wound area reduction in the study time frame and are likely to heal within 12 weeks. Nonhealers did not reach a 50% wound area reduction in the study time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcutaneous O2 Device | Percent Wound Area Reduction | Wound area reduction - visit 1 - healers | 40.75 percent change of wound area (cm^2) | Standard Error 8.26 |
| Transcutaneous O2 Device | Percent Wound Area Reduction | Wound area reduction - visit 3 - healers | 48.64 percent change of wound area (cm^2) | Standard Error 6.82 |
| Transcutaneous O2 Device | Percent Wound Area Reduction | Wound area reduction - visits 4 - healers | 59.91 percent change of wound area (cm^2) | Standard Error 7.55 |
| Transcutaneous O2 Device | Percent Wound Area Reduction | Wound area reduction - visit 2 - nonhealers | 7.59 percent change of wound area (cm^2) | Standard Error 6.32 |
| Transcutaneous O2 Device | Percent Wound Area Reduction | Wound area reduction - visit 3 - nonhealers | -30.07 percent change of wound area (cm^2) | Standard Error 17.25 |
| Transcutaneous O2 Device | Percent Wound Area Reduction | ound area reduction- visit 4 - nonhealers | -11.21 percent change of wound area (cm^2) | Standard Error 14.5 |