PMID- 25703647
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20201209
IS  - 1524-475X (Electronic)
IS  - 1067-1927 (Print)
IS  - 1067-1927 (Linking)
VI  - 23
IP  - 2
DP  - 2015 Mar-Apr
TI  - Topical administration of a connexin43-based peptide augments healing of chronic 
      neuropathic diabetic foot ulcers: A multicenter, randomized trial.
PG  - 203-12
LID - 10.1111/wrr.12275 [doi]
AB  - 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.
CI  - (c) 2015 Authors. Wound Repair and Regeneration published by Wiley Periodicals, 
      Inc. on behalf of The Wound Healing Society.
FAU - Grek, Christina L
AU  - Grek CL
AD  - FirstString Research, Inc., Mount Pleasant, South Carolina.
FAU - Prasad, G M
AU  - Prasad GM
AD  - Pace Clinical Research Center, Bangalore, Karnataka, India.
FAU - Viswanathan, Vijay
AU  - Viswanathan V
AD  - M.V. Diabetes and Research Center, Chennai, Tamil Nadu, India.
FAU - Armstrong, David G
AU  - Armstrong DG
AD  - Southern Arizona Limb Salvage Alliance (SALSA), Department of Surgery, University 
      of Arizona College of Medicine, Tucson, Arizona.
FAU - Gourdie, Robert G
AU  - Gourdie RG
AD  - Virginia Tech Carilion Research Institute, Center for Heart and Regenerative 
      Medicine Research, Roanoke, Virginia.
AD  - Virginia Tech School of Biomedical Engineering and Sciences, Blacksburg, 
      Virginia, and.
AD  - Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, 
      Roanoke, Virginia.
FAU - Ghatnekar, Gautam S
AU  - Ghatnekar GS
AD  - FirstString Research, Inc., Mount Pleasant, South Carolina.
LA  - eng
GR  - R43 DK080567/DK/NIDDK NIH HHS/United States
GR  - R44 DK080567/DK/NIDDK NIH HHS/United States
GR  - 1R43DK080567-01/DK/NIDDK NIH HHS/United States
GR  - 2R44 DK080567 -02/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150429
PL  - United States
TA  - Wound Repair Regen
JT  - Wound repair and regeneration : official publication of the Wound Healing Society 
      [and] the European Tissue Repair Society
JID - 9310939
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Peptides)
RN  - 0 (TRAF3IP2 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Administration, Topical
MH  - Anti-Infective Agents/*administration & dosage/pharmacology
MH  - Connexin 43/*administration & dosage/*pharmacology
MH  - Diabetic Foot/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Peptides
MH  - Prospective Studies
MH  - Surgical Wound Infection/*drug therapy/pathology
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/*administration & 
      dosage/pharmacology
MH  - Wound Healing/*drug effects
PMC - PMC4472499
MID - NIHMS683422
COIS- CONFLICT OF INTEREST Dr. Ghatnekar is an employee of FirstString Research and has 
      ownership in the company and stock options issued by the company. Dr. Grek is an 
      employee of FirstString Research and has stock options issued by the company. 
      Drs. Armstrong and Gourdie are members of the Scientific Advisory Board of 
      FirstString Research and have stock options issued by the company.
EDAT- 2015/02/24 06:00
MHDA- 2016/05/11 06:00
PMCR- 2015/06/18
CRDT- 2015/02/24 06:00
PHST- 2014/09/19 00:00 [received]
PHST- 2015/02/11 00:00 [revised]
PHST- 2015/02/17 00:00 [accepted]
PHST- 2015/02/24 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
PHST- 2015/06/18 00:00 [pmc-release]
AID - 10.1111/wrr.12275 [doi]
PST - ppublish
SO  - Wound Repair Regen. 2015 Mar-Apr;23(2):203-12. doi: 10.1111/wrr.12275. Epub 2015 
      Apr 29.