Application of S26E for Diabetic Foot Ulcer Healing

Study Overview
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Brief Summary
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A randomized, controlled open-label, parallel group study to examine the effectiveness of a local application of the kalahari melon (Citrullus lanatus) seed oil for the healing of non-infected diabetic foot ulcers.

Detailed Description
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This is a randomized, controlled open-label, parallel group study of 12 weeks duration aimed to examine the effectiveness of a local application of the kalahari melon (Citrullus lanatus) seed oil (S26E) for the healing of non-infected chronic (>12 weeks) diabetic foot ulcers. The S26E is a natural extract rich in unsaturated (such as linoleic, oleic, palmitic and static) fatty acids which have shown promise in the promotion of wound healing by modulating the migration and functional properties of inflammatory cells in wound cites as well as the production of inflammatory cytokines. The safety of topical S26E application on human skin has been clinically demonstrated. Eligible participants will be adults patients with diabetes mellitus (DM) type 1 or 2 and chronic (persistent for >12 weeks after initial presentation) neuropathic or neuroischaemic non-infected diabetic foot ulcers. Following recruitment and randomization (on a 1:1 ratio) eligible patients will attend the study site on weekly intervals. After a run-in period of 2 weeks (visits 1-2) during which all participants will receive the optimal standard-of-care for neuropathic/neuroischaemic diabetic ulcers (incl. optimization of glycemic control, off-loading, local debridement as needed, atraumatic surface scrubbing, saline washing and sterile dressing) eligibility will be reassessed. Participants who will continue in the study will receive standard of care (control group) or standard of care plus daily local S26E application on ulcer (intervention group) (visits 3-12). After visit 12 the application of S26E will be terminated and all participants will receive an additional follow up visit 4 weeks later (final visit). Efficacy end-points will be assessed at the end of the of 12 weeks of observation (Visit 12)

Official Title
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A Study of the Effectiveness of Local S26E Extract Application for Diabetic Foot Ulcer Healing

Conditions
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Diabetic Foot, Neuropathic Foot Ulcer, Chronic Diabetic Ulcer of Left Foot (Diagnosis), Chronic Diabetic Foot Ulcer of Right Foot

Intervention / Treatment
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* Other: Standard-of-care for neuropathic/neuroischemic diabetic foot ulcers
* Drug: S26E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or type 2 Diabetes Mellitus Body Mass Index <40 kg/m2 Glycated Hemoglobin (HbA1c) <10% Presence of a diabetic foot ulcer with the following features i) Owing to chronic peripheral sensorimotor diabetic neuropathy, with or without peripheral arterial disease (critical ischemia excluded as indexed by an Ankle-Brachial index <0.4 ) ii) Persistence for >12 weeks iii) Already following an adequate off-loading method Exclusion Criteria: Presence of clinical signs of infection Inability or refusal to follow off-loading methods Ulcer surface area decline by >15% during the run-in period Malignant disease (non-melanoma skin malignancy and healed thyroid malignancies excluded) Acute Charcot arthropathy Serious chronic Hepatic (Child-Pugh B or C), Renal (stage 4-5 CKD) or Heart (NYHA 3-4) disease Known hypersensitivity to the product or its contents Any random glucose measurement >350 mg/dl during the run-in period

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard-of-care managed group<br>This group will receive the optimal standard-of-care for neuropathic/neuroischemic diabetic foot ulcers | Other: Standard-of-care for neuropathic/neuroischemic diabetic foot ulcers<br>* Optimization of glycemic control, off-loading, local debridement as needed, atraumatic surface scrubbing, saline washing and sterile dressing<br>|
| Experimental: S26E<br>This group will receive the optimal standard-of-care for neuropathic/neuroischemic diabetic foot ulcers plus daily S26E application | Other: Standard-of-care for neuropathic/neuroischemic diabetic foot ulcers<br>* Optimization of glycemic control, off-loading, local debridement as needed, atraumatic surface scrubbing, saline washing and sterile dressing<br>Drug: S26E<br>* Daily application of S26E extract on wound site<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ulcer surface area | % change of ulcer surface area | 12 weeks after enrollment in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of completely healed ulcers | Percentage of participants to achieve ulcer healing within the observation period | 12 weeks after enrollment in the study | 
| Incidence of adverse events | Incidence of product-related adverse events (local or systemic infection, local hypersensitivity reactions) | 12 weeks after enrollment in the study | 
| Incidence of amputations | Number of patients that required an amputation | 12 weeks after enrollment in the study |