Background and Rationale Radiation-induced skin injury (RISI) affects approximately 95% of radiotherapy patients in China, with 85% experiencing moderate to severe acute radiation dermatitis (ARD). Current topical treatments have limited efficacy. Akkermansia muciniphila (AKK), a commensal gut bacterium, exhibits anti-inflammatory and barrier-repairing properties via NF-κB, Nrf2, and NLRP3 pathways. This is the first study to apply inactivated AKK topically for RISI.
Detailed Intervention The investigational product is an inactivated whole-cell AKK preparation (provided by State Key Laboratory of Biotherapy, Sichuan University). Participants apply 140 µL per 25 cm² of radiation field (delivering 7 × 10⁷ CFU) three times daily: once 1 hour before each radiotherapy fraction, and twice at other times (e.g., afternoon and bedtime). Treatment begins one day before the first fraction (after baseline skin sampling) and continues until 14 days after the last fraction.
Study Procedures After written informed consent, screening (D-28 to D-1) includes history, physical exam, and ECOG performance status. At baseline (D-1): skin microbiome sampling, digital dermoscopy, RTOG/CTCAE grading, and Skindex-16. During radiotherapy, weekly visits (on the first fraction day of each week, before that fraction) repeat all assessments. Treatment phase duration varies by fraction number (15, 25, 30, or 33 fractions). Follow-up visits occur at days 14, 30, 60, and 90 after the last fraction, with the same assessments. Adverse events are monitored throughout and graded by CTCAE v6.0.
Sample Size Justification Assuming historical incidence of grade ≥2 ARD = 50%, expected incidence with AKK = 30% (one-sided α=0.05, power=80%), the required sample size is 37. Accounting for 8% dropout, final N = 40.
Statistical Analysis Primary analysis uses intention-to-treat population. Incidence of grade ≥2 ARD will be compared to historical control using a one-sample proportion test. Secondary endpoints (skin microbiome, dermoscopy features, Skindex-16, adverse events) will be summarized descriptively with 95% confidence intervals. Continuous variables will be compared using paired t-tests or Wilcoxon signed-rank tests as appropriate.
Data Monitoring A Data Safety Monitoring Committee (DSMC) composed of oncologists, pharmacologists, biostatisticians, and GCP experts will review safety and efficacy data every 6 months and may recommend early termination or protocol modification based on predefined stopping rules (e.g., grade 4 AEs in \>10% of participants).
Ethical Approval The protocol (version 2.0, 4 February 2026) and informed consent form (version 2.0, 4 February 2026) were approved by the Medical Ethics Committee of Jintang County First People's Hospital (approval No. 20260302002, dated 2 March 2026). Any amendments will be submitted for ethical review before implementation.
