A Prospective, Active-Controlled Split-Face Clinical Trial Evaluating the Incremental Aesthetic Benefits of a Glutathione-Containing Booster in a GHK-Conjugated Spicule Regimen

Abstract

Background

Transdermal delivery of hydrophilic peptides such as GHK remains limited by the stratum corneum barrier and the classical 500 Da rule. Spicule-based systems and redox-responsive linkages have been investigated as strategies to enhance epidermal delivery, but in vivo glutathione-triggered cleavage remains a proposed mechanism rather than a clinically proven process.

Objectives

This study aimed to evaluate the clinical efficacy and safety of a GHK-conjugated spicule regimen and to determine whether adding a multi-ingredient, glutathione-containing booster provides incremental aesthetic benefit compared with the shared base regimen alone.

Methods

In this prospective, active-controlled split-face clinical trial, 20 healthy Asian women received five weekly facial treatments. One prespecified facial side received the base regimen consisting of a GHK-conjugated spicule system and base concentrate, while the contralateral side received the same base regimen plus a separate multi-ingredient booster containing 1% glutathione. Wrinkle depth, pore parameters, skin elasticity, dermal density, surface roughness, and pigmentation were evaluated at baseline, after one and three treatment sessions, and 4 weeks after the fifth session. Between-side comparisons were performed using change-from-baseline values, with prespecified primary endpoints, multiplicity adjustment, and effect-size reporting.

Results

Both sides showed improvements from baseline. At the final timepoint, the intensive regimen produced greater improvements than the base regimen in periorbital wrinkle depth (−0.0144 vs. −0.0084 mm), nasolabial wrinkle depth (−0.0227 vs. −0.0173 mm), dermal density (+7.27 vs. +4.49), roughness (−1.23 vs. −0.73 μm), and mean pore volume (−0.0007 vs. −0.0005 mm³). Multiplicity-adjusted between-side differences remained significant for the prespecified primary endpoints and secondary endpoints. No adverse effects were reported.

Conclusion

The GHK-conjugated spicule base regimen improved multiple facial aging indicators, and the booster-inclusive intensive regimen produced statistically greater short-term improvements in this small split-face trial. Because the booster was multi-ingredient and the release mechanism was not directly measured in vivo, these findings should be interpreted as regimen-level clinical evidence rather than proof of glutathione-specific redox cleavage.

Trial Registration

TRN Registration Number: PRE20250909-005