A Randomized Controlled Clinical Trial Protocol of Umbilical Cord Mesenchymal Stem Cell‐Derived Small Extracellular Vesicles for the Treatment of Androgenetic Alopecia in Young Males

Androgenetic alopecia (AGA) is a progressive hair loss disorder affecting young men and significantly impairs psychosocial well-being. Current therapies, including minoxidil and finasteride, have limited efficacy and tolerability. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUCMSC-sEVs) have demonstrated regenerative potential by delivering bioactive molecules that stimulate follicular regeneration. This single-center, prospective, randomized controlled trial will be conducted at Shenzhen People's Hospital. 59 male patients between 18 and 35 years old will be enrolled. In Phase I (dose-escalation), 9 participants will be randomized into three dosing cohorts (1 × 10⁸, 1 × 10⁹, or 1 × 10¹⁰ particles/point intradermally every 2 weeks for 4 times). In Phase II, 50 participants will be randomized 1:1 to hUCMSC-sEVs treatment (optimal dose from Phase I) or topical 5% minoxidil. The primary endpoint is the safety outcomes and the change in terminal hair count/cm² at 24 weeks to determine the best dosage. Secondary outcomes include changes in hair density, shaft diameter, global photographic and dermoscopic assessment, and patient self-assessment. This investigation will determine the best dosage of hUCMSC-sEVs in treatment of androgenic alopecia in young men and evaluate the safety and efficacy of hUCMSC-sEVs compared with minoxidil in young male AGA patients. This is the first randomized climbing test of a controlled clinical trial of hUCMSC-sEVs for young male AGA. Positive findings could establish a novel regenerative treatment for hair restoration. Trial Registration: Clinical Trials: ChiCTR2500109770.