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Periodontitis is characterized by a chronic, multifactorial inflammatory process driven by dysbiotic plaque biofilms. It is recognized as the most common chronic inflammatory non-communicable disease in humans. The advanced and severe forms of periodontitis have an estimated prevalence of 7.4%, while milder forms can affect up to 50% of the population.
If left untreated, periodontitis can lead to tooth loss. However, it is largely preventable and treatable with mechanical non-surgical periodontal therapy. To improve periodontal healing and thus clinical attachment gain after non-surgical therapy, adjunctive bioactive formulations such as enamel matrix derivatives, sodium hypochlorite, locally delivered antimicrobials, or hyaluronic acid have recently been proposed. However, these agents are non-autologous formulations and expensive.
Platelet-rich fibrin (PRF) acts as a scaffold that inhibits the early migration of epithelial cells into the periodontal tissues. Its regenerative properties are primarily due to its ability to promote angiogenesis. This ability is attributed to the 3D fibrin matrix, which can simultaneously transport several cytokines and growth factors. These include vascular endothelial growth factor (VEGF), insulin growth factor (IGF), transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF). PRF further shows antibacterial properties and accelerates soft tissue healing. So far PRF is not routinely used in periodontal non-surgical therapy.
The aim of this 6-month, split-mouth randomized clinical trial including 20 patients is to test whether PRF can improve the results after non-surgical therapy.
The primary objective of this study is to determine whether scaling and root planing (SRP) combined with the application of a platelet-rich fibrin (PRF) membrane can improve clinical outcomes. Specific outcomes to be measured include reduction in probing pocket depth (PPD), gain in clinical attachment level (CAL), improvement in plaque index, gingival index, and minimization of gingival recession (GR) compared to SRP therapy alone after 3 and 6 months. Further patients reported pain outcomes as well as bacterial profiles and inflammatory markers will be checked.
Patients presenting with periodontitis stage II-IV will be included having at least 20 teeth.
The study includes multiple timepoints: a screening visit, a visit for full-mouth non-surgical treatment with and without PRF in a split-mouth design, a 7-day follow-up visit, a 3-month follow-up visit, and a final assessment 6 months after the non-surgical therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control side | Sham Comparator | After non-surgical mechanical debridement of all pockets ≥ 5 mm, an empty syringe will be inserted. |
|
| Test side | Active Comparator | After non-surgical mechanical debridement of all pockets ≥ 5 mm, PRF will be inserted. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRF as adjunct to non-surgical mechanical debridement | Biological | Non-surgical mechanical debridement with hand and power-driven instruments will be performed. Venous blood will be harvested from the patient and centrifuged. Immediately afterwards, the PRF will be inserted in all pockets of the allocated side of the jaw in all pockets ≥ 5 mm. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in PPD after 6 months | Changes in probing depths measured with a periodontal probe in mm from baseline to 6 months after non-surgical periodontal therapy | 6 months follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Change in PPD after 3 months | Changes in probing depths measured with a periodontal probe in mm from baseline to 3 months after non-surgical periodontal therapy | 3 months follow-up |
| Change in clinical attachment level (CAL) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alexandra Stähli, DMD | Contact | +41 79 387 15 14 | alexandra.staehli@unibe.ch | |
| Jean-Claude Imber, DMD | Contact | jean-claude.imber@unibe.ch |
| Name | Affiliation | Role |
|---|---|---|
| Giovanni Salvi, DMD | University of Bern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Periodontology, University of Bern | Recruiting | Bern | 3010 | Switzerland |
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| ID | Term |
|---|---|
| D010518 | Periodontitis |
| D017622 | Periodontal Attachment Loss |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D055093 | Periodontal Atrophy |
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| ID | Term |
|---|---|
| D056690 | Prolactin-Releasing Hormone |
| ID | Term |
|---|---|
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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This is a split-mouth study. One side of the mouth (upper and lower jaw) will be treated with adjunctive PRF during non-surgical mechanical therapy and the other without.
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Opaque sealed envelopes will held the randomisation key of which side has to be treated with PRF. After completion of the non-surgical mechanical debridement in the whole dentition, the sealed envelope will be opened. PRF will be obtained from the elbow vene and after centrifugation the PRF will be applied in the pockets ≥ 5 mm. On the control side an empty cannula will be held.
|
| Control, non-surgical mechanical debridement alone | Biological | Non-surgical mechanical debridement with hand and power-driven instruments will be performed. Venous blood will be harvested from the patient and centrifuged. Immediately afterwards, an empty sy will be inserted in all pockets of the allocated control side of the jaw in all pockets ≥ 5 mm. |
|
The distance in millimeters from the cement-enamel junction (CEJ) to the bottom of the periodontal pocket. This will be assessed using a periodontal probe with mm scale
| 3 months and 6 months follow-up |
| Frequency of residual pockets | The number of probing depth of > 5 mm will be assessed | 3 months and 6 months follow-up |
| Full-mouth bleeding score (FMBS) | Percentage of tooth sites (six sites) revealing the presence of bleeding on probing to the bottom of the periodontal pocket. For this a periodontal probe with mm scale will be used, a score of 0% will represent perfect hygiene and 100% plaque on all surfaces (worst value) | Baseline, 3 months and 6 months follow-up |
| Gingival Recession (REC) | The distance in millimeters from the gingival margin to the cemento-enamel junction (CEJ). The measurements will be performed with a periodontal probe with a mm scale | Baseline, 3 months and 6 months follow-up |
| Comparison in PPD change between smokers and non-smokers | Differences in outcome measures will be assessed | 3 months and 6 months follow-up |
| Levels of periodontal bacteria | Levels of periodontal bacteria will assessed by multiplex Polymerase Chain Reaction | Baseline, 3 months and 6 months follow-up |
| Comparison of periodontal bacteria between smokers and non-smokers | Levels of periodontal bacteria will assessed by multiplex PCR | Baseline, 3 months and 6 months follow-up |
| Levels of Interleukin (IL)-1beta | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Levels of Matrix metalloproteinase (MMP)-8 | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Levels of IL-8 | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Comparison between smokers and non-smokers in levels of IL-1beta | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Comparison between smokers and non-smokers in levels of MMP-8 | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Comparison between smokers and non-smokers in levels of IL-8 | Levels in gingival crevicular fluid will be assessed with ELISA assays | Baseline, 7 days, 3 months and 6 months follow-up |
| Antimicrobial activity of PRF | Remnants of PRF will be used for assessment of antimicrobial activity | At visit of Step-2 therapy, expected to be ca. 2-4 weeks after baseline |
| Comparison between smokers and non-smokers in antimicrobial activity of PRF | Remnants of PRF will be used for assessment of antimicrobial activity | At visit of Step-2 therapy, expected to be ca. 2-4 weeks after baseline |
| Patient reported pain outcomes | A visual analogue scale (100 mm) will be used for the left and right side of the jaw to quantify pain levels. 0 will be no pain at all and 100 mm the worst imaginable level of pain. | Each day from day 1 to 7 after non-surgical periodontal therapy |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |