Phase I study of H5.020CMV.PDGF-beta to treat venous leg ulcer disease.
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SUBMITTER: Margolis DJ
PROVIDER: S-EPMC2835007 | biostudies-literature | 2009 Oct
REPOSITORIES: biostudies-literature
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Phase I study of H5.020CMV.PDGF-beta to treat venous leg ulcer disease.
Margolis David J DJ Morris Lee M LM Papadopoulos Maryte M Weinberg Linda L Filip Jennifer C JC Lang Stephanie A SA Vaikunth Sachin S SS Crombleholme Timothy M TM
Molecular therapy : the journal of the American Society of Gene Therapy 20090728 10
Venous leg ulcers are a prevalent nonhealing wound of the lower extremity. Although topically applied growth factors successfully improve wound repair in animal studies, similar studies on humans with venous leg ulcers have not been successful. This study was designed to evaluate the acute safety and biologic feasibility of peri-ulcer injection of a replication-incompetent adenoviral construct expressing platelet-derived growth factor-beta (PDGF-beta). In this phase I study, we demonstrate the i ...[more]
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Project description:BackgroundVenous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing.Methods/designThis randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks.DiscussionThe ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12614000293662.
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Project description:Venous leg ulcers (VLUs) are often refractory to compression therapy, and their prevalence is increasing. An autologous homologous skin construct (AHSC) that uses the endogenous regenerative capacity of healthy skin has been developed to treat cutaneous defects, with a single application. The ability of AHSC to close VLUs with a single treatment was evaluated in an open-label, single-arm feasibility study to test the hypothesis that AHSC treatment will result in wound closure by providing healthy autologous tissue to the wound bed.MethodsTen VLUs were treated with a single application of AHSC. A 1.5 cm2 full-thickness skin harvest from the proximal calf was collected and sent to a Food and Drug Administration-registered facility, where it was processed into AHSC and returned to the provider within 48 hours. AHSC was spread evenly across the wound and dressed with silicone. The primary endpoint was wound closure rate at 12 weeks. Wound closure was followed with 3-dimensional planimetry, and closure was confirmed by a panel of plastic surgeons. Additional endpoints followed for 12 weeks included graft take, harvest site closure, adverse event rate, complications, and patient-reported pain.ResultsAll 10 VLUs demonstrated successful graft take as evidenced by graft persisting in wound and harvest site closure. Eight VLUs exhibited complete closure within 12 weeks. One VLU that failed to heal with a prior split thickness skin graft closed within 13.5 weeks with AHSC. The mean time of closure was 34 days (95% confidence interval, 14-53). Pain improved by closure confirmation visit. There was 1 serious adverse event unrelated to the product or procedure.ConclusionThis pilot study demonstrated that AHSC may be a viable single-application topical intervention for VLUs and warrants further investigation in larger, controlled studies.
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