Application of S26E for Diabetic Foot Ulcer Healing

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot; Chronic Diabetic Foot Ulcer of Right Foot; Neuropathic Foot Ulcer; Chronic Diabetic Ulcer of Left Foot (Diagnosis)
• Intervention / Treatment: Other: Standard-of-care for neuropathic/neuroischemic diabetic foot ulcers; Drug: S26E

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • Diabetes Clinical Research Laboratory, 1st Department of Propaedeutic Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard-of-care managed group; 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; Optimization of glycemic control, off-loading, local debridement as needed, atraumatic surface scrubbing, saline washing and sterile dressing
Experimental: S26E; 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; Optimization of glycemic control, off-loading, local debridement as needed, atraumatic surface scrubbing, saline washing and sterile dressing; Drug: S26E; Daily application of S26E extract on wound site

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Cheikhyoussef N, Kandawa-Schulz M, Bock R, de Koning C, Cheikhyoussef A, Hussein AA. Characterization of Acanthosicyos horridus and Citrullus lanatus seed oils: two melon seed oils from Namibia used in food and cosmetics applications. 3 Biotech. 2017 Oct;7(5):297. doi: 10.1007/s13205-017-0922-3. Epub 2017 Aug 31.
• Silva JR, Burger B, Kuhl CMC, Candreva T, Dos Anjos MBP, Rodrigues HG. Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair. Mediators Inflamm. 2018 Apr 12;2018:2503950. doi: 10.1155/2018/2503950. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Actual): November 29, 2021
• Study Completion (Actual): November 29, 2021

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 4, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: S26E for neuropathic ulcers

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No