Three-arm randomized controlled trial evaluating the effectiveness of the self-assembling peptide P11-4 in the remineralization of enamel carious white spot lesions: a study protocol.

BACKGROUND

Enamel carious white spot lesions (WSLs) represent early-stage demineralization that may progress to cavitated lesions requiring invasive treatment. The self-assembling peptide P11-4 (SAP P11-4) is a biomimetic agent designed to promote enamel remineralization by forming a biomatrix that attracts calcium and phosphate ions and supports hydroxyapatite formation. Although evidence supports its efficacy, the optimal application protocol remains unclear, and no clinical trial has directly compared single vs. repeated SAP P11-4 application.

OBJECTIVE

To compare the remineralization efficacy of repeated vs. single SAP P11-4 application in adolescents with enamel carious WSLs at the prespecified 6-month primary time point, while also evaluating both SAP P11-4 regimens against fluoride varnish alone over 12 months.

METHODS

This three-arm, partially blinded, randomized controlled trial will enroll participants aged >10 and <18 years with at least two active enamel carious WSLs on smooth surfaces of permanent teeth. Participants will be randomly allocated 1:1:1 to Group A (single SAP P11-4 application + FV), Group B (SAP P11-4 applications at baseline and 3 months + FV), or Group C (FV alone). The planned sample size is 75 participants (25 per group). The primary outcome is the change in the QLF-derived lesion volume parameter (ΔQ) from baseline to 6 months at the lesion level, comparing repeated vs. single SAP P11-4 application. Secondary outcomes include longitudinal changes in QLF measures, fluorescence loss (ΔF), clinical lesion activity assessed using ICDAS II, ICDAS-LAA, and LAA criteria, periodontal parameters, and patient-reported tolerability assessed by visual analogue scale and adverse event recording. QLF assessments will be performed by a blinded investigator. Linear mixed-effects models will account for repeated measurements and multiple lesions nested within patients.

RESULTS

The study was approved by the Bioethics Committee of the Medical University of Warsaw (KB/1/2026, 12 January 2026). Recruitment is planned to commence in February 2026, with study completion expected in July 2027.

CONCLUSIONS

This trial will provide evidence on the comparative efficacy of single vs. repeated SAP P11-4 application and inform an evidence-based clinical protocol for managing enamel WSLs in adolescents.

CLINICAL TRIAL REGISTRATION: https://clinicaltrial.gov/, identifier NCT07664046.