Abstract
BACKGROUND: Lifestyle changes have meant that it is problematic for many people across the globe to maintain adequate vitamin D concentrations. As UV-catalysed production in the skin, which uses vitamin D-binding protein to facilitate systemic absorption, is the primary source of vitamin D, it is questionable if oral supplementation of this vitamin is the optimal means to replace it. However, supplementing an oil-soluble vitamin via the skin is problematic as it gets stuck in the stratum corneum after topical application. This clinical study will test if a new vitamin D ester, vitamin D phosphate, which is more water-soluble compared to vitamin D, administered via a transdermal patch, can be used to improve vitamin D status. METHOD: This is a two-part study comprising a dose-escalation with the vitamin D phosphate transdermal patch followed by a randomised, double-blind, placebo-controlled, multiarmed, multistage clinical trial. It is a single-centred, 12-week study that will enrol a maximum of 100 participants. The dose escalation study will monitor safety and tolerability using serum calcium and 25(OH)D(3) levels. The blinded, randomised trial will test different dose frequencies for 4 weeks compared to a placebo. Then, after an interim analysis, the best dosing frequency will be assessed against a placebo. The primary outcome for the multistage clinical study will be the percentage change in 25(OH)D(3) concentration in the serum (ng/mL) at weeks 4 and 8 compared to baseline. The secondary outcome measures include percentage change in serum vitamin D-binding protein levels, skin interstitial fluid biomarker concentrations, and nail appearance after 4 and 8 weeks compared to baseline. DISCUSSION: This study will determine if a vitamin D phosphate transdermal patch can improve vitamin D status. In addition, it could provide a better understanding of how vitamin D is absorbed directly into the skin after application by measuring the serum vitamin D-binding protein and skin biomarker responses to transdermal supplementation. TRIAL REGISTRATION: Clinical Trials.gov NCT06098846, registered on 23rd October 2023.