Safety and efficacy of topical melatonin add-on in healing of diabetic foot ulcer: a double blind, randomized clinical trial

Diabetic foot ulcer (DFU) is one of the disturbing complications associated with diabetes that influence the quality of life. Melatonin with stimulating of collagen production, emerges as a promising candidate for chronic wound treatment such as diabetic foot ulcer (DFU). This clinical trial investigates the efficacy of a novel topical melatonin hydrogel in promoting the healing process of DFUs. To assess the efficacy of the topical hydrogel containing 1% melatonin on grades 1 and 2 DFUs, a double-blind, randomized, placebo-controlled trial was designed. Subjects were randomly assigned to two groups: an experimental group receiving melatonin (1 mg/cm²) and a control group receiving a placebo. The hydrogel was applied at night for two months. The number, grade, size, and healing proportion of ulcers were assessed at baseline, after one month (day 30), and at the end of the study (day 60). Thirty patients with a total of fifty-three ulcers completed the study. The melatonin group demonstrated a significant decrease in ulcer number and severity grade, along with an increase in healing proportion compared to the placebo group (p < 0.05). The reduction in ulcer size in the melatonin group was approximately twofold greater in compare with the placebo (mean reduction: -2.7 ± 0.4 cm² vs. -1.34 ± 0.39 cm²; p-value: 0.08). Patients on melatonin with HbA1c levels ≤ 8% or with new-onset ulcers (≤ 3 weeks old) experienced statistically significant reductions in ulcer size (p = 0.02 and 0.04, respectively). Topical 1% melatonin hydrogel demonstrated efficacy and safety in reducing the number, grade, and size of DFUs when used as a complementary therapy alongside standard ulcer care. This approach may help prevent complications associated with non-healing ulcers thereby improving patients’ quality of life and functional independence. (Trial Id:54495; Iranian registry of clinical trial identifier code: IRCT20200220046560N1; registration date: 2021-04−09).