HPTC Versus AFSM in Diabetic Foot Ulcers

NCT07781917 | Not Yet Recruiting FDA Device

• 1 other identifier: AIMS/IEC/275/2026
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a randomized controlled clinical investigation in patients suffering from diabetic foot ulcers at multiple centres in India and Bangladesh. The study compares patient outcomes using standard wound care with a High Purity Type-I Collagen-Based Skin Substitute against standard wound care with an Acellular Intact Fish Skin Matrix.

Conditions

Diabetic Foot Ulcer (DFU)

Keywords

Diabetic Foot Ulcer;; High Purity Type-I Collagen-Based Skin Substitute;; Acellular Intact Fish Skin Matrix;; Randomized Controlled Clinical Trial;; Multicentric Study;

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving Confirmed Complete Wound Closure

  Complete wound closure is defined as 100% epithelialization of the target ulcer with no drainage and no clinically evident open area requiring dressing, confirmed by a blinded central adjudicator at a follow-up visit approximately 7 days after initial clinical closure is observed.

  Up to Week 13 (initial closure assessed through Week 12; confirmation visit approximately 7 days later)

Secondary Outcomes (8)

• Percentage Wound Area Reduction Over Time

  Weeks 2, 4, 6, 8, and 12

• Proportion Achieving ≥50%, ≥75%, and ≥90% Wound-Area Reduction

  Week 12

• Time to Confirmed Complete Wound Closure

  Up to Week 13

• Mean Number of Study-Product Applications

  Up to Week 6

• Number of Participants with Adverse Events

  Up to Week 13

Other Outcomes (4)

• Tissue Advanced Glycation End-Product Accumulation (CML)

  Baseline (Day 0) and Day 5

• Quantitative Collagen Organization and Maturation

  Baseline (Day 0) and Day 5

• Microvessel Density and Vascular Maturation

  Baseline (Day 0) and Day 5

Study Arms (2)

High Purity Type-I Collagen-Based Skin Substitute and SOC

ACTIVE COMPARATOR

The SOC in this study is wound care covering with High Purity Type-I Collagen-Based Skin Substitute (Helicoll®) applied weekly or as needed, followed by a padded 3-layer dressing (non-adherent porous paraffin gauze; absorbent gauze pads; soft roll and compressive crepe bandage).

Device: High Purity Type-I Collagen-Based Skin Substitute and SOC

Acellular Intact Fish Skin Matrix and SOC

ACTIVE COMPARATOR

The SOC in this study is wound care covering with Acellular Intact Fish Skin Matrix (Kerecis Omega3 Wound®) applied weekly or as needed, followed by the same padded 3-layer dressing described above.

Device: Acellular Intact Fish Skin Matrix and SOC

Interventions

High Purity Type-I Collagen-Based Skin Substitute and SOC DEVICE

Arm A - The SOC in this study is wound care covering with High Purity Type-I Collagen-Based Skin Substitute (Helicoll®) applied weekly or as needed followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous paraffin gauze, second layer - absorbent gauze pads \& third layer - soft roll and compressive wrap (crepe bandage). For participants enrolled in the optional histopathological sub-study, a 2-mm punch biopsy will be obtained from the wound edge at baseline and on Day 5 under local anesthesia. Specimens will be fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 4 μm for histological and immunohistochemical analysis.

Also known as: Helicoll, HPTC

High Purity Type-I Collagen-Based Skin Substitute and SOC

Acellular Intact Fish Skin Matrix and SOC DEVICE

Arm B - The SOC in this study is wound care covering with Acellular Intact Fish Skin Matrix (Kerecis Omega3 Wound®) applied weekly or as needed followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous paraffin gauze, second layer - absorbent gauze pads \& third layer - soft roll and compressive wrap (crepe bandage). For participants enrolled in the optional histopathological sub-study, a 2-mm punch biopsy will be obtained from the wound edge at baseline and on Day 5 under local anesthesia. Specimens will be fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 4 μm for histological and immunohistochemical analysis.

Also known as: AFSM, Intact Fish Skin Graft

Acellular Intact Fish Skin Matrix and SOC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be at least 18 years of age or older.
• Subjects must have a diagnosis of type 1 or 2 diabetes mellitus.
• Diabetic foot ulcer located below the malleoli, Wagner Grade 1 or 2 (University of Texas Grade 1-2), without exposed bone.
• Target ulcer present for a minimum of 4 weeks, with post-debridement area of approximately 5-20 cm².
• Failure to achieve ≥30% ulcer-area reduction during the run-in period, or an equivalent documented waiver (Section 12.1).
• Adequate circulation to the affected foot: ankle-brachial index (ABI) between 0.7 and 1.3 (or alternative vascular criteria per protocol).
• Glycated haemoglobin (HbA1c) ≤ 12%.
• The subject must consent to using the prescribed off-loading method for the duration of the study.
• The subject must agree to attend the scheduled study visits required by the protocol.
• The subject must be willing and able to participate in the informed consent process.
• Patients must have read and signed the IEC-approved ICF before screening procedures are undertaken.

You may not qualify if:

• A subject known to have a life expectancy of less than 6 months.
• If the target ulcer is infected or if there is cellulitis in the surrounding skin.
• Presence of osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence; Wagner Grade ≥3.
• A subject that has an infection in the target ulcer that requires systemic antibiotic therapy.
• A subject receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy.
• Topical application of steroids to the ulcer surface within one month of initial screening.
• A subject with a previous partial amputation on the affected foot, if the resulting deformity impedes proper offloading of the target ulcer.
• A subject with glycated haemoglobin (HbA1c) greater than 12% at or within 3 months of the initial screening visit.
• A subject with an acute Charcot foot, or an inactive Charcot foot that impedes proper offloading of the target ulcer.
• Women who are pregnant or considering becoming pregnant within the next 6 months.
• A subject with end-stage renal disease requiring dialysis; active malignancy.
• A subject who participated in a clinical trial involving treatment with an investigational product within the previous 30 days.
• A subject who, in the opinion of the investigator, has a medical or psychological condition that may interfere with study assessments.
• A subject treated with hyperbaric oxygen therapy or a cellular and/or tissue product (CTP) in the 30 days prior to the initial screening visit.
• Known hypersensitivity to HPTC or its components; known fish allergy/hypersensitivity for participants who would be allocated to AFSM.

Sponsors & Collaborators

• EKAGRA Health, Dhaka: collaborator
• Adichunchanagiri Institute of Medical Sciences, B G Nagara: lead
• Mysore Medical College and Research Institute, Mysurur: collaborator
• National Institute of Burn & Plastic Surgery, Dhaka: collaborator

Study Sites (4)

National Institute of Burn & Plastic Surgery

Dhaka, 1000, Bangladesh

Location

EKAGRA Health

Dhaka, 1209, Bangladesh

Location

Adichunchanagiri Institute of Medical Sciences

Mandya, Karnataka, 571448, India

Location

Mysore Medical College and Research Institute

Mysore, Karnataka, 570001, India

Location

Related Publications (6)

• Narayan N, Gowda S, Shivannaiah C. A Randomized Controlled Clinical Trial Comparing the Use of High Purity Type-I Collagen-Based Skin Substitute vs. Dehydrated Human Amnion/Chorion Membrane in the Treatment of Diabetic Foot Ulcers. Cureus. 2024 Dec 5;16(12):e75182. doi: 10.7759/cureus.75182. eCollection 2024 Dec.

  PMID: 39649230 BACKGROUND

• Narayan N, Shivaiah R, Kumar V, Kumar KM, Chethan S, Gowda S. Comparative Efficacy of High Purity Type I Collagen-Based Skin Substitute and Dehydrated Human Amnion/Chorion Membrane in Diabetic Foot Ulcers: A Multicentre Randomized Controlled Trial. Cureus. 2025 Oct 19;17(10):e94952. doi: 10.7759/cureus.94952. eCollection 2025 Oct.

  PMID: 41122365 BACKGROUND

• Lullove EJ, Liden B, Winters C, McEneaney P, Raphael A, Lantis Ii JC. A Multicenter, Blinded, Randomized Controlled Clinical Trial Evaluating the Effect of Omega-3-Rich Fish Skin in the Treatment of Chronic, Nonresponsive Diabetic Foot Ulcers. Wounds. 2021 Jul;33(7):169-177. doi: 10.25270/wnds/2021.169177. Epub 2021 Apr 14.

  PMID: 33872197 BACKGROUND

• Lantis Ii JC, Lullove EJ, Liden B, McEneaney P, Raphael A, Klein R, Winters C, Huynh RN. Final efficacy and cost analysis of a fish skin graft vs standard of care in the management of chronic diabetic foot ulcers: a prospective, multicenter, randomized controlled clinical trial. Wounds. 2023 Apr;35(4):71-79. doi: 10.25270/wnds/22094.

  PMID: 37023475 BACKGROUND

• Dardari D, Piaggesi A, Potier L, Sultan A, Diener H, Francois M, Dorweiler B, Bouillet B, M'Bemba J, Chaillous L, Clerici G, Kessler L, Wetzel-Roth W, Storck M, Davidsson OB, Baldursson B, Kjartansson H, Lantis JC, Charpentier G. Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers. NEJM Evid. 2024 Dec;3(12):EVIDoa2400171. doi: 10.1056/EVIDoa2400171. Epub 2024 Oct 4.

  PMID: 39365895 BACKGROUND

• Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson D, Vohra S, White IR, Boutron I. CONSORT 2025 statement: updated guideline for reporting randomised trials. Lancet. 2025 Apr 14:S0140-6736(25)00672-5. doi: 10.1016/S0140-6736(25)00672-5. Online ahead of print.

  PMID: 40245901 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Prema Dhanraj, MS, MCh

  Rajarajeshwari Medical College and Hospital

  STUDY CHAIR

Central Study Contacts

Naveen Narayan

CONTACT

9980023372; naveennumerouno@gmail.com

Chethan Shivannaiah

CONTACT

8277520509; drrschethan@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: August 24, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months after publication of the primary manuscript
• Access Criteria: Requests should be directed to the corresponding author (Dr. Naveen Narayan, naveennumerouno@gmail.com) with a methodologically sound research proposal. Data will be provided after de-identification, subject to a signed data-access agreement, and following approval of the proposal by the trial investigator group.

Locations

BA (2); IN (2)