A Multistage, Multiarmed, Double-Blind Placebo-Controlled Human Transdermal Vitamin D Supplement Study (TransVitD)

Abstract

Background: Life-style changes have meant that it is problematic to maintain adequate vitamin D concentrations in many people across the globe. Given that it's mainly generated by UV-catalysed production in the skin where it uses vitamin D binding protein to facilitate systemic absorption., it is questionable if oral administration of this vitamin is the optimal means to replace it. However, supplementing this oil-soluble vitamin is problematic as it gets stuck in the stratum corneum after topical application. This clinical study will test the ability of a new vitamin D ester, vitamin D phosphate, which is more water-soluble compared to vitamin D, can be administered via a transdermal patch 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, multi-armed, multi-stage clinical trial. It is a single-centred, 12-week study that will enrol a maximum of 100 participants. The blinded, randomised trial will test different dose frequencies for four weeks compared to a placebo, then after an interim analysis, the best dosing frequency will be assessed against a placebo. The dose escalation study will monitor safety and tolerability using serum calcium levels. The primary outcome for the multi-stage clinical study will be the concentration of 25(OH)D3 in the serum (ng/mL) at weeks 4 and 8 compared to baseline. The secondary outcome measures include 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 after application directly to the skin by measuring the serum vitamin D binding protein and skin biomarker responses to transdermal supplementation. Trial Registration: Clinical Trials .gov NCT06098846, registered on 23^rd October 2023