Examining the Effectiveness of DermGEN™ in the Treatment of Diabetic Foot Ulcers in First Nations People

Study Overview
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Brief Summary
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The study will examine the effectiveness of a decellularized dermal matrix (i.e., DermGEN™) in improving wound healing, quality of life and associated costs of treatment of DFUs in First Nations people living in the Northwestern Ontario Communities. First Nations people with active diabetic foot (DFU) ulcer attending a wound care clinic located at the Rainy River district office. An interventional, two-arm, randomized, prospective study of (1) standard of care (control) vs. (2) DermGEN™ - a decellularized dermal matrix (treatment) will be used in the treatment and management of DFU. Patients will be randomized to each arm (n=60 per arm) based on power calculations using data from our Pilot study.

Official Title
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Examining the Effectiveness of DermGEN™ Versus Standard of Care in the Treatment of Diabetic Foot Ulcers in First Nations People Living in Northwestern Ontario Communities

Conditions
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Diabetes Mellitus, Ulcer Foot, Ulcer Healing, Diabetic Foot Ulcer, Non-healing Wound, Wound of Skin, Wound; Foot, Tissue Injury

Intervention / Treatment
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* Procedure: Standard of Care
* Other: DermGEN™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant and social support (e.g., family, caregiver) ready and willing to participate and comply with follow-up regime Participant willing to be involved in self-care (e.g., keep dressing dry at home) required during treatment Participant willing to wear Total Contact Cast (TCC) for wound off-loading during treatment Participant or legal representative has read and signed the informed consent form Documented stable Type I or II diabetes (HbA1C between 5.0 to 10 mmol/L within 1 month prior to Day 0) Ulcer has been present for a minimum of 2 weeks as of Day 0 Ulcer area is ≥2 cm2 prior to debridement at Day 0 of study Ulcer extends through dermis and into subcutaneous tissue but without exposure of muscle, tendon, bone or joint capsule Ulcer is free of dead tissue and clinical infection, and is comprised of healthy vascular tissue suitable for skin grafting on Day 0 Adequate perfusion to the extremity determined by at least one of the following: Palpable pedal pulses, Transcutaneous oxygen measurement at the dorsum of the foot ≥30 mm Hg, Ankle-brachial index ranging from 0.8 to 1.2, At least biphasic Doppler arterial waveforms at the dorsalis pedis and posterior tibial arteries Exclusion Criteria: The individual has any condition that seriously compromises their capacity to provide consent and answers questions related to this study. Untreated infection of soft tissue or bone and/or autoimmune connective tissue disorders Ulcer is over Charcot deformity (joints deformity of foot and ankle common in people with diabetes) Body mass index ≥50 kg/m2 Ulcer is not classified as diabetes-related Ulcer has tunnels or sinus tracts that cannot be completely debrided Medical condition(s) that in the investigators' opinion make the patient inappropriate for study (e.g active liver disease) Presence of malignant disease not in remission for 5 years or more The individual is undergoing chemotherapy/radiation therapy The individual received radiation therapy within 30 days of Day 0 of study The individual is taking an immunosuppressant medication (e.g., corticosteroids, immunosuppression or cytotoxic agents), or is anticipated to require such agents during study Presence of acute or chronic hepatitis, liver disease, anemia, serum albumin <2.0 gm/dL, or has alkaline phosphatase or LDH at twice the normal upper limit Obvious clinical signs and symptoms of ongoing tissue infection (i.e., cellulitis) or bone infection (i.e., osteomyelitis) Female individuals are pregnant at time or intend to get pregnant during study time The individual has known allergies to antibiotics, such as penicillin and streptomycin The individual is an active smoker (smoke one or more cigarette a day) The individual has a history of a bleeding disorder or is taking blood thinner medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: An interventional, two-arm, randomized, prospective study of (1) standard of care (control) vs. (2) DermGEN™ - a decellularized dermal matrix (treatment) will be used in the treatment and management of DFU. Patients will be randomized to each arm (n=60 per arm) based on power calculations using data from our Pilot study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>The standard of care includes physical examination, wound debridement, total cast or offloading boot, non-adherent dressing (PolyMem®) for wound covering, weekly visit for ongoing assessment | Procedure: Standard of Care<br>* debridement, wound dressings, offloading<br>|
| Experimental: DermGEN™<br>A decellularized dermal matrix created from donated human skin. This arm will receive the same care as the Standard of Care control arm-physical examination, wound debridement, total cast or offloading boot, non-adherent dressing (PolyMem®) for wound covering, weekly visit for ongoing assessment-with the addition of DermGEN™ onto the wound at the first visit. | Other: DermGEN™<br>* Decellularized human dermal matrix created from donated human skin<br>* Other names: Acellular Dermal Matrix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean and median reduction in wound area in the first 4 weeks | Mean and Median reduction in wound area in comparison to Treatment day 0. Area measured with Silhouette® measurement camera. | 4 weeks | 
| Proportion with complete healing in the first 8 weeks | Proportion with complete healing in the first 8 weeks. (Complete healing is defined as 100% epithelialization without drainage.) | 8 weeks | 
| Proportion with complete healing in the first 12 weeks | Proportion with complete healing in the first 12 weeks. (Complete healing is defined as 100% epithelialization without drainage.) | 12 weeks | 
| Incidence of adverse events. | Number of adverse events observed for each arm divided by participants in each arm, reported as a percentage | Reports included at any time up to and including 20 weeks post treatment. | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 1 week | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 2 weeks | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 3 weeks | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 4 weeks | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 8 weeks | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 12 weeks | 
| Impact of Treatment on Wound - LUMT Score | Impact of treatment as measured by Leg Ulcer Management Tool (LUMT) score. Comparing initial LUMT score on treatment day 0 to subsequent weeks. | 20 weeks | 
| Impact of Treatment on Quality of Life (WoundQoL) | Impact of treatment on Quality of Life using the WoundQoL questionnaire score. Comparison of score on treatment day 0 to subsequent weeks. | 4 weeks | 
| Impact of Treatment on Quality of Life (WoundQoL) | Impact of treatment on Quality of Life using the WoundQoL questionnaire score. Comparison of score on treatment day 0 to subsequent weeks. | 8 weeks | 
| Impact of Treatment on Quality of Life (WoundQoL) | Impact of treatment on Quality of Life using the WoundQoL questionnaire score. Comparison of score on treatment day 0 to subsequent weeks. | 12 weeks | 
| Impact of Treatment on Quality of Life (WoundQoL) | Impact of treatment on Quality of Life using the WoundQoL questionnaire score. Comparison of score on treatment day 0 to subsequent weeks. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion with complete healing at any time point | Number of wounds closed (Complete healing is defined as 100% epithelialization without drainage)at any time divided by the number of participants in each arm reported as a percentage | up to and including 20 weeks post initial treatment (Day 0) | 
| Time to first-measured complete healing | Time to first-measured complete healing (Complete healing is defined as 100% epithelialization without drainage) | up to and including 20 weeks post initial treatment (Day 0) | 
| Mean and median reduction in wound area at 8 weeks | Mean and Median reduction in wound area in comparison to Treatment Day 0. Area measured with Silhouette® measurement camera. | 8 weeks | 
| Mean and median reduction in wound area at 12 weeks | Mean and Median reduction in wound area in comparison to Treatment Day 0. Area measured with Silhouette® measurement camera. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Ulcer, Diabetic Foot Ulcer, Non-healing Wound, Tissue Engineering, Regenerative Medicine, Decellularized Matrix, Acellular Dermal Matrix, Tissue Allograft, Indigenous Healing, Advanced Wound Care