A UV-Free Strategy for Vitamin D Synthesis in Skin: Concept Verification and a Randomised Double-Blind Placebo-Controlled Clinical Trial of a Cholecalciferol Phosphate Patch (TransVitD)

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Abstract

DESIGN: Laboratory and animal work was followed by a dose-finding study and a randomised, placebo-controlled, double-blind clinical trial (allocation 1:1:1:1). SETTING: A single-centre study conducted in London, UK, with dosing over winter months. PARTICIPANTS: 108 healthy volunteers between 18 and 65 years of age with suspected low vitamin D levels. INTERVENTION: Cholecalciferol phosphate patch. MAIN OUTCOME MEASURES: Safety: blood calcium levels. Efficacy: Percentage change in the concentration of serum 25(OH)D3 compared to baseline. RESULTS: In animals and ex vivo human skin, cholecalciferol phosphate penetrates the tissue and converts to cholecalciferol (vitamin D3). Biological responses mimic ultraviolet radiation (UVR) skin exposure, upregulating the vitamin D-binding protein (VDBP) in rodents and improving systemic vitamin D status without associated skin inflammation or DNA damage. In Part 1 of the clinical study, lasting 4 weeks, 16 participants were enrolled in two dose-escalating cohorts (total doses of 5 mg and 31 mg). Across both cohorts, two participants reported local skin irritation, but serum calcium and 25(OH)D3 did not change. A total of 92 participants were randomised in Part 2, lasting eight weeks; 30 were allocated to active arm A and 29 to placebo, and both arms continued to 8 weeks, whilst two arms, active B and active C, were stopped after 4 weeks. Seventy-three participants completed their final study visit and 19 discontinued. Comparing active arm A (total dose = 140 mg) with placebo, the per-protocol percentage change from baseline in 25(OH) D3 was +19.9 percentage points (95% CI -1.3 to +41.0; p = 0.065). In the modified intention-to-treat population (n = 54), the baseline adjusted difference in serum 25(OH)D3 at 8 weeks was +0.52 ng/mL (95% CI -2.18 to +3.22; p = 0.71). Adverse skin irritation events were reported by 42.9% of active and 42.3% of placebo participants (p = 1.00). CONCLUSION: A cholecalciferol phosphate patch generated vitamin D in the skin in animals without UV exposure. In humans, the patch was safe but did not improve vitamin D status; the benefit was not greater than approximately 3 ng/mL (300-500 IU/day of oral cholecalciferol). TRIAL REGISTRATION: ClinicalTrials.gov NCT06098846.

Abstract as published, via PubMed.