Akkermansia Muciniphila (AKK) for Radiation-Induced Skin Injury (AKK-RIS)

Clinical Application of AKK Bacterial Preparation for the Treatment of Radiation-Induced Skin Injury

This study is a multicenter, open-label, Phase I single-arm clinical trial evaluating the safety and tolerability of a topical AKK probiotic preparation (Akkermansia muciniphila) for the prevention and treatment of radiation-induced skin injury in patients receiving radiotherapy for breast cancer, head and neck cancer (including nasopharyngeal carcinoma). A total of 40 participants are planned to receive the AKK preparation applied to the radiation field three times daily, starting one day before the first radiotherapy fraction and continuing until 14 days after the last fraction. The primary outcome is the incidence of grade ≥2 acute radiation dermatitis (ARD) assessed by RTOG and CTCAE criteria. Secondary outcomes include changes in skin micro-features under digital dermoscopy, skin microbiota composition, quality of life (Skindex-16), and safety.

Study Overview

• Status: Recruiting
• Conditions: Radiation-Induced Skin Injury
• Intervention / Treatment: Biological: AKK Topical Preparation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Xeulei Ma; Phone Number: +8613408410416; Email: drmaxuelei@gmail.com
    • Chengdu, Sichuan, China, 610400
      • Recruiting
      • Jintang County First People's Hospital
      • Contact: Lei Zhang; Phone Number: +8618908070191; Email: 314189929@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of breast cancer, head and neck cancer (including nasopharyngeal carcinoma) receiving radiotherapy
• Age ≥18 years and ≤75 years, any sex
• Signed written informed consent
• Radiation field skin area can be localized and skin inflammation can be assessed
• ECOG performance status 0-1, life expectancy ≥3 months
• Adequate major organ function
• Fertile patients (both sexes) must use effective medical contraception during the study and for 6 months after the last dose
• Willing to comply with follow-up and skin image collection

Exclusion Criteria:

• Cognitive impairment preventing understanding of the study
• Use of antibiotics or antifungals within 1 month
• Previous treatment with other bacterial preparations
• Participation in other bacterial therapy trials
• Any abnormality (e.g., scar, tattoo) in the radiation field that would interfere with assessment
• Allergy to probiotics or any component of the study preparation; history of severe allergic reactions (e.g., anaphylaxis, angioedema, respiratory distress, allergic purpura, Arthus reaction)
• Use of immunosuppressive drugs
• Symptomatic or rapidly progressive central nervous system metastases, extensive lung metastases causing dyspnea, tumor invading major vessels or nerves
• Poorly controlled cardiac disease (NYHA class ≥2 heart failure, unstable angina, myocardial infarction within 1 year, clinically significant arrhythmia requiring treatment)
• Pregnancy or breastfeeding
• Active tuberculosis, bacterial or fungal infection (grade ≥2 per CTCAE), or HIV infection
• Substance abuse or psychiatric disorder
• Active autoimmune disease or history thereof (exceptions: vitiligo, childhood asthma fully resolved with no intervention in adulthood)
• History of alcohol or drug abuse
• Planned pregnancy from screening until 12 months after last treatment
• Any concomitant condition that, in the investigator's judgment, would compromise patient safety or study completion
• Any other condition deemed unsuitable for enrollment by the investigator
• Inability to provide written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: AKK Topical Preparation

Biological: AKK Topical Preparation; Inactivated whole-cell Akkermansia muciniphila topical preparation. Dose: 140 µL per 25 cm² of radiation field (7 × 10⁷ CFU). Applied 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 radiotherapy fraction (after baseline skin sampling) and continues until 14 days after the last radiotherapy fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade ≥2 Acute Radiation Dermatitis	Proportion of participants developing grade 2 or higher acute radiation dermatitis (ARD) as assessed by RTOG and CTCAE v6.0 criteria during radiotherapy and follow-up.	From first radiotherapy fraction up to 90 days after the last fraction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Skin Micro-Features on Digital Dermoscopy	Evolution of skin micro-features (e.g., erythema, scaling, vascular changes) observed by digital dermoscopy during treatment and follow-up.	Baseline, weekly during radiotherapy, and at days 14, 30, 60, 90 after last radiotherapy fraction.
Skin Microbiota Composition	Changes in the relative abundance of skin bacterial species measured from desquamated scale samples.	Same as above.
Frequency of Grade ≥3 Acute Radiation Dermatitis	Proportion of participants developing grade 3 or higher ARD assessed by RTOG/CTCAE v6.0.	From first radiotherapy fraction to 90 days after last fraction.
Duration of Grade 2/3/4 Acute Radiation Dermatitis	Number of days from first onset to resolution of grade 2, 3, or 4 ARD.	During radiotherapy and up to 90 days after last fraction.
Incidence of Grade 2 ARD at 2 Weeks Post-Radiotherapy	Proportion of participants with grade 2 ARD at 14 days after the last radiotherapy fraction.	Day 14 after last radiotherapy fraction.
Frequency of Local Infection	Occurrence of clinically diagnosed infection within the irradiated skin area.	From first radiotherapy fraction to 90 days after last fraction.
Other Adverse Events	Type, frequency, severity, and relationship to study treatment of adverse events graded by CTCAE v6.0.	From informed consent to 90 days after last radiotherapy fraction.

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Head and Neck Cancer; Radiation-Induced Skin Injury; Akkermansia muciniphila; Acute Radiation Dermatitis; AKK; Topical Probiotic
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Head and Neck Neoplasms
• Other Study ID Numbers: 20260302002; AKK-RIS-2025-V2.0 (Other Identifier: Jintang County First People's Hospital and West China Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No