Abstract
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 NCT 06098846