The Effectiveness of the Self-Assembling Peptide P11-4 in the Remineralization of Enamel Carious White Spot Lesions

Official title

A Three-arm Randomized Controlled Trial Evaluating the Effectiveness of Self- Assembling Peptide P11-4 in the Remineralization of Enamel Carious White Spot Lesions

Overview

This is three-arm Randomized Controlled Trial. The main goal is to evaluate the effectiveness of self-assembling peptide P11-4 (SAP P11-4) in the remineralization of enamel carious white spot lesions. Participants with carious white spot lesions will be assigned to one of three study groups and remineralisation agents will be applied according to the study protocol. The primary objective is to assess changes in the carious white spot lesions over time using quantitative light-induced fluorescence and clinical evaluation.

Detailed description

This study will be conducted at an academic center. Recruitment will include patients aged 10 to 18 years presenting with carious white spot lesions on the smooth surfaces of permanent teeth at the Department of Pediatric Dentistry, Medical University of Warsaw. The planned study duration is 1 year. After assessment of the inclusion and exclusion criteria and enrollment into the study, participants will undergo randomization and will be allocated to 1 of 3 study groups.

Group A will receive a single application of Curodont Repair (self-assembling peptide P11-4) at the first visit, together with fluoride varnish application every 3 months (Duraphat Fluoride Varnish, Colgate, 22,600 ppm fluoride). Group B will receive repeated applications of Curodont Repair at the first visit, after 3 months, together with fluoride varnish application every 3 months. Group C, the control group, will receive only fluoride varnish every 3 months.

There is currently limited evidence regarding the effectiveness of repeated applications of remineralization agents containing self-assembling peptide P11-4. In addition, this study includes a relatively long follow-up period, allowing evaluation of the durability of the treatment effect over time.

At each follow-up visit, scheduled every 3 months, white spot lesions will be assessed using quantitative light-induced fluorescence (QLF) and visual clinical examination.

Interventions

• Other Self-assembling peptide P11-4
  Self-assembling peptide P11-4 will be applied on enamel carious white spot lesions according to the study protocol. In the single-application group (group A), the agent will be applied once at the first visit(baseline). In the repeated-application group (group B), the agent will be applied at the first visit (baseline) and after 3 months.
• Other Fluoride varnish
  Fluoride varnish will be applied every 3 months according to the study protocol.

Primary outcome measures

• Change in Fluorescence Loss (ΔF) of White Spot Lesions From Baseline to 12 Months Assessed by Quantitative Light-Induced Fluorescence [Time frame: baseline and 12 months follow-up]
• Change in lesion volume ΔQ of White Spot Lesions From Baseline to 12 Months Assessed by Quantitative Light-Induced Fluorescence [Time frame: from baseline to the 12-month follow-up]

Secondary outcome measures (11)

• Change in QLF Fluorescence Loss (ΔF) of White Spot Lesions From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Change in Lesion Area of White Spot Lesions From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Change in QLF Lesion Volume (ΔQ) of White Spot Lesions From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Mean ICDAS II Score From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Mean ICDAS-Lesion Activity Assessment Score From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Number of Lesions in Each Nyvad Lesion Activity Assessment Category From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Mean Plaque Index Score From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Mean Gingival Index Score From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Percentage of Sites With Bleeding on Probing From Baseline to Each Follow-up Visit [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Mean Visual Analogue Scale Score for Patient-reported Tolerability [Time frame: Baseline, 3 months, 6 months, 9 months, and 12 months]
• Number of Adverse Events Throughout the Study Period [Time frame: Baseline through 12 months]

Eligibility criteria

Inclusion criteria

• Age >10 years and <18 years.
• Presence of at least 2 active enamel carious white spot lesions on a smooth tooth surface (labial/buccal surfaces of permanent teeth) based on International Caries Detection (ICDAS II) and Assessment System -Lesion Activity Assessment (ICDAS-LAA), and Lesion Activity Assessment (LAA criteria).
• Tooth eligible for treatment:

• Vital pulp,
• no loss of hard dental tissues within the investigated lesion (ICDAS II) code 1 or 2 , LAA code 1, ICDAS-LAA>7;
• QLF score parameters consistent with demineralization without loss of tissue continuity- code 1 or 2),
• no history of trauma to the tooth.
• Systemically healthy patient.
• No contraindications to the use of fluoride preparations.
• No fixed orthodontic appliance.
• Written consent for participation in the study signed by the legal guardian, or by the legal guardian and the patient.

Exclusion criteria

• Systemic diseases or chronic medication use due to chronic conditions.
• Viral/bacterial illness on the day of the visit, e.g., herpetic stomatitis, influenza, tonsillitis (temporary restriction).
• Pregnancy or breastfeeding.
• Allergy to any component of the SAP P11-4 preparation or the fluoride varnish.
• Professional fluoride prophylaxis performed <3 months ago.
• Presence of cavitation (loss of hard tissues) in the treated tooth - ICDAS II code ≥3, ICDAS-LAA<7, LAA code 0, 2-9.
• Carious WSL previously treated with the Icon resin infiltrant (methacrylate resin).
• Developmental enamel defects.
• Patient undergoing orthodontic treatment with fixed appliances.
• Inability to ensure regular follow-up visits.
• Lack of cooperation from the guardian or the patient.
• Refusal to participate in the study and/or absence of written consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Poland · 1 center

• University Clinical Center of the Medical University of Warsaw, Department of Pediatric De — Warsaw

Publications

• ÜÇTAŞLI, M. B., AKGÜL, S., UYSAL, G. Ç., AHISHA, C. D., KESKİN, A. Ş., & TOPBAŞ, N. K. (2025). SCIENTIFIC FOUNDATIONS AND CLINICAL DIRECTIONS IN DENTISTRY: REMINERALIZATION, RADIATION AND RESTORATION. In SCIENTIFIC FOUNDATIONS AND CLINICAL DIRECTIONS IN DENTISTRY: REMINERALIZATION, RADIATION AND RESTORATION. Zenodo. https://doi.org/10.5281/zenodo.15670487
• Parums DV. Editorial: The 2024 Revision of the Declaration of Helsinki and its Continued Role as a Code of Ethics to Guide Medical Research. Med Sci Monit. 2024 Dec 1;30:e947428. doi: 10.12659/MSM.947428. PMID 39616449
• Hussain U, Kunwar SS, Khan UW, Kamran MA, Thakfan AS, Alshahrani OA, Rehman A, Niazi FH, Shah AM, Alam S, Campobasso A. Efficacy of various interventions for the management of white spot lesions associated with fixed orthodontic treatment: a systematic review and network meta-analysis of randomized controlled trials. BMC Oral Health. 2026 Feb 21;26(1):358. doi: 10.1186/s12903-026-07755-3. PMID 41723426
• Soliman EM, Abdelfattah WM, Mohamed DR, Nagui DA, Holiel AA. Clinical evaluation of the remineralizing potential of biomimetic scaffolds on enamel white spot lesions: A 12-month randomized controlled trial. J Dent. 2026 Mar;166:106303. doi: 10.1016/j.jdent.2025.106303. Epub 2025 Dec 16. PMID 41412271
• Sawair FA, Ryalat S, Shayyab M, Saku T. The unstimulated salivary flow rate in a jordanian healthy adult population. J Clin Med Res. 2009 Oct;1(4):219-25. doi: 10.4021/jocmr2009.10.1267. Epub 2009 Oct 16. PMID 22461872
• Loe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Nov-Dec;38(6):Suppl:610-6. doi: 10.1902/jop.1967.38.6.610. No abstract available. PMID 5237684
• Patel JS, Shin D, Willis L, Zai A, Kumar K, Thyvalikakath TP. Comparing gingivitis diagnoses by bleeding on probing (BOP) exclusively versus BOP combined with visual signs using large electronic dental records. Sci Rep. 2023 Oct 10;13(1):17065. doi: 10.1038/s41598-023-44307-z. PMID 37816902
• Elaziz BSA, Hamdy D, Galal M, Khattab NMA. The remineralizing ability of self-assembling peptide P11-4, 2% arginine enriched sodium fluoride and functionalized tri calcium phosphate fluoride varnishes in treatment of white spot lesions - a randomized controlled trial. BDJ Open. 2025 Jul 27;11(1):70. doi: 10.1038/s41405-025-00353-5. PMID 40715066

Identifiers

NCT: NCT07664046 · CURODONT-WSL-2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗