Randomized Clinical Trial investigating Self-Assembling Peptide P11-4 for Treatment of Early Occlusal Caries

Abstract

Non-invasive caries treatment is a major focus in modern dentistry. The present study was designed to evaluate the effectiveness of monomeric self-assembling peptide P 11-4 (SAP P 11-4) in combination with fluoride varnish or polymeric self-assembling peptide matrix (SAPM) in treatment of non-cavitated occlusal caries. Ninety children and adolescents were included in this randomized, gold-standardcontrolled clinical trial. Test Group 1 received SAP P 11-4 and twice fluoride varnish at baseline and Day 180, Test Group 2 received SAP P 11-4 on baseline and twice weekly SAPM (home-application), and Control Group received fluoride varnish on baseline and Day 180. Caries progression was measured by laser fluorescence, Nyvad Caries Activity, ICDAS-II-codes, and investigator assessments. Laser fluorescence changes demonstrated superior results for Test Group 1 and 2, as values decreased compared to an increase for the Control Group (p < 0.0005). ICDAS-II codes at Day 360 showed partial regression for Test Group 1 (6.7%) and Test Group 2 (20.0%) and partial progression for Control Group (23.3%) (p < 0.01). Nyvad Caries Activity yielded superior caries inactivation for Test Groups, compared to Control Group (p = 0.002). This trial showed that SAP P 11-4, applied either in combination with fluoride varnish or twice weekly SAPM, was a superior treatment for early caries compared to fluoride varnish alone. Caries levels have significantly decreased over the past decades, partially due to the introduction of fluoride in various forms 1. However, despite the promising efforts and results worldwide, caries levels have remained high, and caries is still the most common disease worldwide 2. Recent efforts to lower caries levels have focused on treating early carious lesions non-invasively, as there is consensus that only early intervention, prior to cavitation, can lead to a regression of the caries to a more healthy state 3,4. Novel therapeutics have been called for, and promising approaches are based on biomimetic research and development. Biomimetic concepts fall into two categories, either based on amelogenin or derivatives thereof, or on rationally designed and screened systems 5,6. There is substantial research in the field, yet most of it is in vitro-based. The exceptions are recent clinical investigations of the rationally designed self-assembling peptide P 11-4 applied either in its monomeric form (SAP P 11-4) 5,6 or its polymeric form as a self-assembled peptide matrix (SAPM). This is the first clinical trial investigating the combined effect of SAP P 11-4 and SAPM in treatment of early carious lesions. SAP P 11-4 has been systematically investigated 7. The self-assembling peptide was rationally designed to provide favourable physicochemical characteristics for nucleation of hydroxyapatite (HA) on the surface of the formed fibres of the 3D matrix 8,9. The mechanism of action of SAP P 11-4 in the remineralization of enamel was proposed early on and has been proven since 10,11. When monomeric SAP P 11-4 is applied onto th...

Efficacy of P11-4 for the treatment of initial buccal caries: a randomized clinical trial

“…The combination treatment inactivated 80-100% of the carious lesions and caused regression into a lower ICDAS-II class in up to 30% of cases. In contrast, in the control groups solely receiving fluoride varnish, only 35% of the carious lesions were inactivated, and 6% regressed to smaller ICDAS-II class 17 and 20% needed restorative treatment during the 12 months study period 18 .…”

“…Another early clinical trial has shown that, when SAP P 11 -4 is applied on proximal carious surfaces, it leads to an arrest or even regression of caries in 85% of cases as judged by standardized clinical radiographs 16 . Recent randomized gold-standard controlled clinical trials have shown SAP P 11 -4 combined with fluoride varnish or a Self-Assembling Peptide Matrix Gel to be superior for the treatment of early occlusal caries compared to fluoride varnish alone 17,18 . The combination treatment inactivated 80-100% of the carious lesions and caused regression into a lower ICDAS-II class in up to 30% of cases.…”

Impact of self-assembling peptides in remineralisation of artificial early enamel lesions adjacent to orthodontic brackets

“…The authors concluded that treatment of initial carious lesions with P 11 -4 led to better remineralisation of the subsurface lesions compared with the control teeth. Doberdoli et al 15 investigated the effectiveness of both monomeric self-assembling peptide P 11 -4 and the polymeric self-assembling peptide matrix in treatment of non-cavitated occlusal caries in children. The study showed that P 11 -4, applied either in combination with fluoride varnish or twice weekly as a gel was a superior treatment for early caries lesions, when compared to application of fluoride varnish alone.…”

“…Recently, biomimetic remineralisation strategies such as self-assembling peptides are considered to be a new perspective in caries prevention 13 – 15 . It is reported that the self-assembling peptide P 11 -4 forms a three dimensional matrix within the subsurface body of an initial enamel lesion and mimics enamel matrix proteins 16 , 17 .…”

Identification of Key Functional Motifs of Native Amelogenin Protein for Dental Enamel Remineralisation

“…P11-4 has since then been developed into a novel peptide based therapeutic for dental caries by inducing mineralisation. It was patented and marketed as Curodont TM Repair and is now widely available for the treatment of dental caries [ 72 ].…”