A Novel Proline-rich Peptide Hydrogel for Periodontal Regeneration in Adult Periodontitis Patients

Официальное название

A Novel Proline-rich Peptide Hydrogel for Periodontal Regeneration: a Multicenter Parallel-arm Randomized Clinical Trial

Обзор

The goal of this clinical trial is to learn if a novel peptide-rich hydrogel works to achieve periodontal regeneration in adults. It will also learn about the safety of the hydrogel. The main questions it aims to answer are: * Does the novel peptide hydrogel achieve periodontal regeneration to a similar degree as another currently used therapy (hyaluronic acid)? * What medical problems, if any, do participants have when receiving the novel hydrogel treatment? Researchers will compare the novel peptide hydrogel to another commonly used hydrogel (hyaluronic acid) to see if the peptide hydrogel works to treat periodontal bone defects. Participants will: * Receive the novel hydorgel or hyaluronic acid when they undergo periodontal regenerative surgery * Visit the clinic at regular intervals for 1 year after the surgery for follow ups

Подробное описание

The primary objective of this study (PICOS) is to compare, in adult periodontitis patients (P), the efficacy of a P-HA hydrogel (PeriHeal) (I) to that of a commercial HA hydrogel (hyaDENT BG) (C) for the regenerative treatment of intrabony defects based on CAL changes (O) after 6 and 12 months in a RCT (S).

Additional objectives are to assess (a) changes in secondary clinical and radiographic outcomes, (b) patient-reported outcomes (PROs), and (c) molecular outcomes based on proteomic analysis of gingival crevicular fluid (GCF) (see details below).

The null hypothesis (H0) is that there are no statistically significant differences between P-HA and HA hydrogels in terms of CAL after 6 and 12 months.

The primary outcome is CAL change 6 and 12 months after regenerative surgery. Secondary outcomes measured 6 and 12 months after regenerative surgery include changes in: probing pocket depth (PPD), bleeding on probing (BoP), recession (REC), and MBL. Post-operative wound healing and patient-reported symptoms will be assessed 7 and 14 days after surgery. Patients' oral health-related quality of life (OHRQoL) will be assessed at baseline and 6 and 12 months after surgery. GCF collected at 7, 14 and 30 days after surgery will be analysed using mass spectrometry-based proteomics.

Вмешательства

• Биопрепарат Hydrogel
  A novel cross-linked HA hydrogel incorporating proline-rich peptides (PeriHeal, Corticalis AS, Oslo, Norway) has been developed to enhance periodontal wound healing and regeneration.
• Биопрепарат Hydrogel
  Hyaluronic acid is currently used in periodontal regenerative surgery as a hydrogel mixture of cross-linked (1.6%) and natural (0.2%) HA of bacterial origin, marketed as hyaDENT BG (Regedent AG, Zurich, Switzerland)

Первичные конечные точки

• CAL change [Срок оценки: 6 and 12 months after periodontal regenerative surgery]

Вторичные конечные точки (4)

• MBL change [Срок оценки: 6 and 12 months after regenerative periodontal surgery]
• Gingival Healing Index (GHI) [Срок оценки: 7 and 14 days after periodontal regenerative surgery]
• Oral health related quality of life [Срок оценки: 6 and 12 months after regenerative surgery]
• Proteomic analysis of gingival crevicular fluid (GCF) [Срок оценки: 7, 14 and 30 days after regenerative surgery]

Критерии участия

Критерии включения

• Adults >18 years with periodontitis (Stage III or IV)
• Systemically healthy (ASA I or II)
• Non-smokers or smoking <10 cigarettes/day
• Having undergone steps 1 (risk factor control, oral hygiene improvement including interdental hygiene) and 2 (subgingival instrumentation and biofilm control) of systematic periodontal therapy
• Indication for step 3 periodontal therapy, i.e., sites with residual/persistent pockets (PPD >5 mm and BoP or PPD >6 mm) around single- or multi-rooted teeth with mobility <grade II at re-evaluation 8-12 weeks after non-surgical instrumentation (Step 2). Further site-specific criteria include at least one site with a radiographic infrabony defect (2- or 3-walled) with a >3 mm intrabony component, not associated with an open furcation, indicated for regenerative surgery
• Full-mouth plaque score (FMPS) and full-mouth bleeding score (FMBS) ≤20% before surgery

Критерии исключения

• Medical conditions contraindicating surgery
• Pregnancy or lactation
• Current use of systemic antibiotics
• Smoking >10 cigarettes/day
• FMPS or FMBS >20%
• Mobility grade II or greater
• Acute oral infections, active endo-perio lesions or active carious lesions on teeth associated with bone defects

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Норвегия · 1 центр

• Faculty of Dentistry, University of Oslo — Oslo

Испания · 1 центр

• Faculty of Dentistry, University Complutense of Madrid — Madrid

Публикации

• Zhu H, Gomez M, Xiao J, Perale G, Betge F, Lyngstadaas SP, Haugen HJ. Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation. ACS Appl Bio Mater. 2020 Apr 20;3(4):2263-2274. doi: 10.1021/acsabm.0c00064. Epub 2020 Mar 13. PMID 35025278
• Ovrebo O, Lyngstadaas SP, El Khassawna T, Jamous R, Ma Q, Munoz F, Permuy M, Cantalapiedra AG, Serrano-Munoz AJ, Ramis JM, Monjo M, Rossi F, Haugen HJ. Multiomics Comparison of Proline-Rich Peptide-Enhanced Hyaluronic Acid Gels Versus Conventional Regenerative Materials: An Early Wound-Healing Model. J Periodontal Res. 2025 Oct;60(10):1018-1038. doi: 10.1111/jre.70032. Epub 2025 Sep 10. PMID 40928114
• Villa O, Wohlfahrt JC, Mdla I, Petzold C, Reseland JE, Snead ML, Lyngstadaas SP. Proline-Rich Peptide Mimics Effects of Enamel Matrix Derivative on Rat Oral Mucosa Incisional Wound Healing. J Periodontol. 2015 Dec;86(12):1386-95. doi: 10.1902/jop.2015.150207. Epub 2015 Aug 7. PMID 26252748
• Saiz AM, Rahmati M, Johnson SD, Bhat AS, Baldini TD, Ovrebo O, Nogueira LP, Khassawna TE, Stotzel S, Fierro FA, Lee MA, Leach JK, Haugen HJ. Systemic versus local delivery of mesenchymal stem cells to improve the early stages of fracture healing in a polytrauma model. J Biol Eng. 2025 Sep 30;19(1):82. doi: 10.1186/s13036-025-00554-4. PMID 41029699
• Saiz AM, Rahmati M, Baldini TD, Satish Bhat A, Johnson SD, Liu M, Reyes RM, Fok SW, Lee MA, El Khassawna T, Wieland DCF, Marinho AL, Blanchet C, Leach JK, Haugen HJ. Mesenchymal stem cells delivered via a bioactive disordered peptide-hydrogel platform modulate early inflammation and enhance skeletal repair in a polytrauma model. J Tissue Eng. 2025 Dec 1;16:20417314251397106. doi: 10.1177/204173142 PMID 41340773
• Lyngstadaas SP, Wohlfahrt JC, Brookes SJ, Paine ML, Snead ML, Reseland JE. Enamel matrix proteins; old molecules for new applications. Orthod Craniofac Res. 2009 Aug;12(3):243-53. doi: 10.1111/j.1601-6343.2009.01459.x. PMID 19627527

Идентификаторы

NCT: NCT07581613 · PERIHEAL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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