Acellular Dermal Allograft for Chronic Diabetic Wounds

The purpose of this study is to determine the efficacy of a novel decellularized dermal matrix (DDM) DermGEN™ for the treatment of diabetic foot ulcers (DFU). Despite several advances in wound treatments, hard-to-heal wounds, such as diabetic foot ulcer, still require 12 to 16 weeks to achieve complete closure. Although the focus of most research into wound-healing treatments has been on moisture and bacterial control, new approaches that target the instability of the extracellular matrix (ECM) in a wound are timely and much needed, particularly for hard-to-heal wounds such as DFUs. Innovative technologies that provide ECM interactions halt the chronic inflammatory cycle and stimulate cells that allow for tissue regeneration and wound healing. DermGEN™ is a human dermal allograft that has been minimally processed from human skin to remove epidermal and dermal cells while preserving the structure and intrinsic properties of the natural extracellular matrix of the dermis. This has potential to facilitate a shorter wound-healing time.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot Ulcer; Wound Heal
• Intervention / Treatment: Other: decellularized dermal matrix

Detailed Description

DermGEN™ is a human dermal allograft that has been minimally processed from human skin to remove epidermal and dermal cells while preserving the structure and intrinsic properties of the natural extracellular matrix of the dermis. The resulting sterile decellularized scaffold provides a support for cellular repopulation and vascularization at the surgical site to facilitate integumental wound healing. Unlike other tissue-derived ECM-based products, such as acellular and decellularized matrices where treatments require anywhere from 6 to 10 reapplications of the product to achieve wound-closure rates of only 35% to 55% (16) DermGEN™ only requires one. A feasibility study has shown that 82% of participants (9 of 11 subjects) who had their DFU (1 ulcer/participant) treated with a single application of DDM (DermGEN) achieved complete wound closure between 2 and 8 weeks, with a mean 3.3 weeks and median of 2.3 weeks (https://doi.org/10.1016/j.jcjd.2022.03.010). The investigators have used this technology on a number of cases with good success. The investigators wish to gather further data with this study.

The purpose of this clinical trial is to perform a pilot study to determine the efficacy of DermGEN in the treatment in acute and non-healing diabetic foot ulcers (DFU). This will be a one-arm prospective study. It is hypothesized that DermGEN treatment will result in positive healing outcomes with no significant adverse effects. We anticipate to enroll 30 patients.

After enrolment and an initial assessment (time 0 data), participants will be treated with a single application of the DDM following standard-of-care procedures that include debridement of the DFU to provide healthy bleeding tissue margins. Then, it is applied with the dermal side in contact with the ulcer bed and covered by a bolster dressing. The bolster dressing is changed weekly during the follow-up. Follow-up assessments are conducted at 1, 2, 3, 4, 12 and 20 weeks. Digital photography is used to capture the appearance and size of the ulcer at each visit.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Graham Roche-Nagle, MD; Phone Number: 416-340-5332; Email: Graham.Roche-Nagle@uhn.ca
• Study Contact Backup: Name: Naomi Eisenberg, MEd; Phone Number: 8623 416-340-4800; Email: Naomi.Eisenberg@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
      • Contact: Graham Roche-Nagle, MD; Phone Number: 416-340-5332; Email: Graham.Roche-Nagle@uhn.ca
      • Contact: Naomi Eisenberg, MEd; Phone Number: 8623 416-340-4800; Email: Naomi.Eisenberg@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A subject will be considered eligible to participate in this study if each of the following inclusion criteria is satisfied:

1. Patient's ulcer has been present for a minimum of 2 weeks as of Day 0.
2. Study ulcer has healed <30% in size during the 2 weeks prior to Day 0.
3. Ulcer area is ≥1 cm2 prior to debridement at Day 0 of study.
4. Ulcer extends through dermis and into subcutaneous tissue but without exposure of muscle, tendon, bone or joint capsule.
5. Ulcer is free of necrotic debris and clinical infection, and is comprised of healthy vascular tissue suitable for skin grafting on Day 0.
6. Patient has adequate circulation to the foot as evidenced by toe pressure measurement.
7. Female patients are not pregnant at time of, or during study.
8. Patient and caregiver ready and willing to participate and comply with follow-up regime.
9. Patient or legal representative has read and signed the Institutional Ethics Review Board approved informed consent form.

Exclusion Criteria:

A subject will not be considered eligible to participate in this study if any one of the following exclusion criteria is satisfied:

1. Evidence of gangrene on affected foot.
2. Ulcer is over Charcot deformity (fractures or dislocation).
3. Ulcer is non-diabetic in etiology.
4. Patient receiving oral or parenteral corticosteroids, immunosuppression or cytotoxic agents, or is anticipated to require such agents during study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dermgen; Application of Dermgen	Other: decellularized dermal matrix; Application of Wound bed; Other Names: Dermgen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Healing	Percentage of Wound Area Reduction Compared to Baseline	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound healing	Percentage of Patients with Complete Healing at Any Time Point	1 year
Adverse events	Number of Patients With Adverse Events	20 weeks
Ulcer Reoccurrence	Number of Patients with Ulcer Reoccurrence in the Same Location after Complete Healing	1 year

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Graham Roche-Nagle, MD, University Health Network, Toronto

Publications and helpful links

General Publications

• Costa IG, Glazebrook M, Lu S, McLaren AM, Gratzer PF. A Feasibility and Safety Study of a Novel Human Decellularized Dermal Matrix to Accelerate Healing of Neuropathic Diabetic Foot Ulcers in People With Type 1 and Type 2 Diabetes. Can J Diabetes. 2022 Apr 6:S1499-2671(22)00073-9. doi: 10.1016/j.jcjd.2022.03.010. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Estimated): January 29, 2024

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; Wounds and Injuries
• Other Study ID Numbers: 23-5933

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
• product manufactured in and exported from the U.S.: No