Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers

A multicenter, randomized trial

Christina L. Grek, G. M. Prasad, Vijay Viswanathan, David G Armstrong, Robert G. Gourdie, Gautam S. Ghatnekar

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signalling accelerates wound reepithelialization. In a prospective, randomized, multicenter clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C-terminus of Cx43, alpha connexin carboxy-terminal (ACT1), in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care (SOC) protocols. Adults with DFUs of at least four weeks duration were randomized to receive SOC with or without topical application of ACT1. Primary outcome was mean percent ulcer reepithelialization and safety variables included incidence of treatment related adverse events (AEs) and detection of ACT1 immunogenicity. ACT1 treatment was associated with a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks (72.1% vs. 57.1%; p-=-0.03). Analysis of incidence and median time-to-complete-ulcer closure revealed that ACT1 treatment was associated with a greater percentage of participants that reached 100% ulcer reepitheliazation and a reduced median time-to-complete-ulcer closure. No AEs reported were treatment related, and ACT1 was not immunogenic. Treatment protocols that incorporate ACT1 may present a therapeutic strategy that safely augments the reepithelialization of chronic DFUs.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalWound Repair and Regeneration
Volume23
Issue number2
DOIs
StatePublished - Mar 1 2015

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Topical Administration
Connexin 43
Diabetic Foot
Multicenter Studies
Ulcer
Peptides
Standard of Care
Foot Ulcer
Therapeutics
Safety
Connexins
Incidence
Clinical Protocols
Wound Healing
Randomized Controlled Trials
Skin
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Dermatology
  • Surgery

Cite this

Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers : A multicenter, randomized trial. / Grek, Christina L.; Prasad, G. M.; Viswanathan, Vijay; Armstrong, David G; Gourdie, Robert G.; Ghatnekar, Gautam S.

In: Wound Repair and Regeneration, Vol. 23, No. 2, 01.03.2015, p. 203-212.

Research output: Contribution to journalArticle

Grek, Christina L. ; Prasad, G. M. ; Viswanathan, Vijay ; Armstrong, David G ; Gourdie, Robert G. ; Ghatnekar, Gautam S. / Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers : A multicenter, randomized trial. In: Wound Repair and Regeneration. 2015 ; Vol. 23, No. 2. pp. 203-212.
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