BACKGROUND: Despite significant advances, the treatment of diabetic foot ulcers (DFUs) remains a major therapeutic challenge for clinicians, surgeons, and other health care professionals. There is an urgent need for new strategies with clinically effective inter-ventions to treat DFUs to reduce the burden of care in an efficient and cost-effective way. OBJECTIVE: This randomized trial evaluated and compared the clinical effectiveness, tolerability, and costs of clostridial collagenase ointment (CCO) de-bridement to that of debridement using saline mois-tened gauze (SMG) and selective sharp debridement for the treatment of DFUs METHODS: Randomized, controlled, parallel group, multicenter, open-label, 12-week study of 48 patients with neuropathic DFUs randomized to 4 weeks of treatment with either CCO or SMG after baseline surgical debridement. The primary end point was the condition of the ulcer bed at the end of treatment as measured using a standardized wound assessment tool. Secondary end points were the percentage of reduction in wound area and therapeutic respo-nse rates. Adverse events were monitored for the tolerability analysis. In addition, a comparative cost-effectiveness analysis was performed from the per-spective of the Centers for Medicare and Medicaid Services as a payer. RESULTS: Both the CCO and SMG groups had significantly improved wound assessment scores after 4 weeks of treatment (CCO, --2.5, P -- 0.007; SMG, --3.4, P -- 0.006). Only CCO treat-ment resulted in a statistically significant decrease from baseline in the mean wound area at the end of treatment (P -- 0.0164) and at the end of follow-up (P -- 0.012). In addition, the CCO group exhibited a significantly better response rate at the end of follow-up compared with the SMG group (0.92 vs 0.75, P < 0.05). Reported adverse events were similar between the 2 treatment groups. None of the reported adverse events were considered to be related to treatment. The economic analysis indi-cated that the direct mean costs per responder in the physician office setting of care were $832 versus $1042 for the CCO group versus the SMG group, whereas the direct mean costs per responder in the hospital outpatient department setting were $1607 versus $1980.
This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu<sup>3</sup>- A(1-7) ( DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers ( n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks' once-daily topical treatment with 0.03% DSC127 ( n = 26), 0.01% DSC127 ( n = 27), or Placebo ( n = 24), followed by 20 weeks' standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log-linear pattern for both intent-to-treat and per-protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo-treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03% DSC127 ( p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers.
BACKGROUND: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats.
OBJECTIVE: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway.
RESEARCH DESIGN AND METHODS: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing.
RESULTS AND CONCLUSIONS: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01295177.
BACKGROUND & OBJECTIVES: Diabetic foot ulcers are the most common cause of non-traumatic lower extremity amputations in developing countries. The aim of this pilot study was to evaluate the safety of using a polyherbal formulation in healing diabetic foot ulcers in comparison with standard silver sulphadiazine cream among patients with type 2 diabetes.
METHODS: A total of 40 (M:F=29:14) consecutive type 2 diabetes patients with foot ulcers were enrolled in this study. They were randomly assigned to two groups of 20 each; Group 1 was treated with polyherbal formulation and group 2 with silver sulphadiazine cream. All the patients were followed up for a period of 5 months. The baseline ulcer size was noted and photograph of the wound was taken at the baseline and at each follow up visit. Number of days taken for healing of the wound was recorded.
RESULTS: The mean age of patients, duration of diabetes and HbA1c% were similar in both the study groups. The mean length and width of the ulcers was also similar in both the groups at baseline visit. There was a significant decrease in the size of the wound (length and width) in both the study groups (P<0.001). The mean time taken for the healing of the ulcer was around 43 days in both groups.
INTERPRETATION & CONCLUSIONS: Diabetic wound cream prepared by using polyherbal formulation was found to be effective as well as safe in healing diabetic foot ulcers like the standard silver sulphadiazine cream.
