A double-blind, placebo-controlled cross-over study to assess the efficacy of topical calcipotriol (Psorcutan®-ointment containing 0.05 µg/g calcipotriol) to improve wound healing in dystrophic epidermolysis bullosa (DEB)Completed
|Project lead||Assoc Prof Dr Martin Laimer, Assoc Prof Dr Roland Lang|
|Organisation||EB House Austria, Salzburg, AUSTRIA|
|Project budget||EUR 20,000.00|
|Start date / Duration||01. Jul 2016 / 27 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria|
|Research area||Symptom prevention & relief|
Short lay summary
Chronic wounds represent a major burden to recessive dystrophic epidermolysis bullosa (RDEB) patients. The hormone vitamin D3 (VD3) plays a critical role in skin homeostasis including wound healing and tissue repair. VD3 has also anti-tumour properties, which is potentially relevant for this patient group, as tumours tend to develop at sites of chronic wounding. Based on previously gathered preclinical evidence, we conducted a phase II clinical study to investigate the effect of topical treatment with an ointment containing a low dose of calcipotriol, an analogue of active VD3, on wound healing, itch, pain, and microbial colonisation in DEB. The results showed that low-dose calcipotriol treatment is safe, can accelerate wound healing, and provides significant relief from burdensome itch.
Owing to genetic defects in structural proteins, skin and mucous epithelia of RDEB patients are prone to blistering and chronic wounding upon minor mechanical stress. Chronic wounds are further associated with excessive pruritus and high risk of malignant transformation. Based on previous preclinical work, we sought to evaluate the safety and efficacy of a low-dose calcipotriol ointment in promoting wound healing and reducing itch and pain in patients with DEB. Eligible DEB patients were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate the efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within 4 weeks of treatment. Secondary objectives included an assessment of safety and the impact of treatment on pruritus, pain, and bacterial wound colonization in patients. While the trial aimed to include 15 participants, only 12 could be recruited. From these, six completed the clinical trial and were included into the final analysis. Notably, reasons for patient drop-out were unrelated to the study, and no severe adverse effects related to treatment were observed at any point during the trial. At day 14, treatment with the low-dose calcipotriol ointment led to a significant reduction in wound area compared to placebo. No significant differences in wound closure between treatment arms could be noted at day 28. Patients reported a significant reduction of pruritus with calcipotriol ointment compared to placebo over the entire course of the treatment. Treatment with low-dose calcipotriol did not affect serum calcium levels and improved the species richness of the wound microbiome, albeit with no statistical significance. These results demonstrate that topical treatment with low-dose calcipotriol significantly reduces itch, accelerates wound healing, and can be safely implemented into the daily wound care of DEB patients.
Enhancing wound healing is expected to not only improve patients’ quality of life, but also significantly reduce cancer risk, as aberrant wound healing and tumor development are tightly intertwined processes in RDEB. Thus, it is important to evaluate drugs with wound healing and anti-neoplastic potential, such as vitamin D3, in controlled clinical trials in order to gain market approval for use in EB.