Perio Protect - Clinical Research

Mark S. Putt, MSD, PhD, Howard M. Proskin, PhD. Custom Tray Application of Peroxide Gel as an Adjunct to Scaling and Root Planing in the Treatment of Periodontitis: A Randomized, Controlled Three-Month Clinical Trial. The Journal of Clinical Dentistry. 2012 March(XXIII-Number 2): 48-56.

CONCLUSION: The adjunctive use over three months of 1.7% hydrogen peroxide gel, locally administered using prescription customized trays in the treatment of subjects with moderate to advanced periodontitis, demonstrated statistically significant clinical improvements in pocket depths and bleeding when compared with SRP alone.

Click here for the full text online article.

_______________________________________________________

C.M. Mitchell, D. Keller, L. Weaks, B. Sindelar. 6-Month Multi-clinic Treatment of Periodontal Disease Using Topical Oxidizing Agents - abstract link.

OBJECTIVES: Determine whether use of PerioProtect Method ® (PPM) in combination with scaling and root-planing (SRP) over 6-months would result in improvements in outcome measures in patients with periodontal disease (PD).

METHODS: 44 patients with mild to severe PD were treated by 4 dentists in separate clinics. Dentists were specially trained in PerioProtect® system. Subject distribution was: Dentist-1, 11 patients (7 male; ages 5213); Dentist-2, 15 patients (3 male; ages 5715); Dentist-3, 15 patients (4 male; ages 5514); Dentist-4, 3 patients (1 male; ages 4920). All patients underwent baseline evaluation for PPD per tooth (6 sites per tooth) and BoP (dichotomous per site). Prior to treatment all patients received instruction on supra-gingival care and the use of PPM. Each Dentist administered a specific combination of PPM and SRP treatment: Group A (7 male; 9 female; age 5313) received whole mouth SRP prior to use of PPM and Group B (7 male; 21 female; age 5514) received PPM first followed by site-specific SRP. Changes in PPD and BoP for all patients were reassessed after a 6 month period.

RESULTS: Baseline averages indicated no significant difference in PPD between Groups A and B (p>0.232); however there was significantly more BoP in patients in Group A at baseline than Group B (p=0.003). At 6 months, PPD values for 0-5mm pockets for all patients significantly improved from baseline (p<0.001) and differences between Dentists were not significant (p>0.360). At 6 months all patients had significantly decreased BoP (p<0.01) with no significant differences noted between Dentists (p>0.556) or between treatment Groups (p>0.361).

CONCLUSIONS: An appropriately trained general Dentist can effectively administer PPM. PPM is effective for improving PPDs and BoP within 6 months in mild to moderate cases of periodontal disease regardless of whether full mouth SRP is followed by PPM or PPM is followed by site-specific SRP.

Click here for the research poster presentation.

_______________________________________________________

T Dunlap, DC Keller, M Marshall, JW Costerton, C Schaudinn, BJ Sindelar, and JR Cotton. Subgingival Delivery of Oral Debriding Agents: A Proof of Concept. The Journal of Clinical Dentistry. 2011 November(XXII-Number 5):149-158.

CONCLUSION: The prescription Perio Tray® effectively placed medication in the gingival sulcus. Mathematical modeling indicated Perio Tray® placement of hydrogen peroxide gel in periodontal pockets with depths up to 9 mm over 15 minutes treatment time was theoretically possible. Pathology reports reveal reductions in subgingival bacterial loads and improvements in pretreatment pocket depths of up to 8 mm after 1.7% hydrogen peroxide and Vibramycin Syrup were prescribed for use with the Perio Tray®. The in vitro analysis indicating that hydrogen peroxide is the active and effective oral debriding agent needs to be confirmed with additional studies.

Click here for the full text online article.

_______________________________________________________

Keller DC. How to Manage Oral Biofilm. Dental Products Report. 2010 July(7):54-55.

Radiographs and charts from this case study indicate that medication placed into periodontal pockets with the prescription Perio Tray® helped decrease bleeding, and reduce pocket depths for a patient who had struggled with gum disease for years. The patient had had two previous rounds of surgical procedures, including bone recontouring, and was recommended to have all lower anterior teeth extracted. In an effort to save his teeth, he opted for treatment with the Perio Protect Method® which included delivery of medication with prescription Perio Trays®. After treatment, bleeding and pocket depths decreased and additional bone support is also evident. With the gain in bone support, the lower anterior teeth did not need to be extracted.

Click here for the full text online article.

_______________________________________________________

Schaudinn C, Gorur A, Sedghizadeh P, Costerton J, and Keller D. Manipulation of the microbial ecology of the periodontal pocket. World Dental 2010 Feb-March: 14-18.

The data suggest that the biofilm potential is an accurate indicator of the microbiological health of the sulcus, and further suggest that the efficient delivery of antibacterial oxidants via the Perio Protect system, which uses an oxidative chemical strategy before the physical removal of the biofilms by scaling and root planing (SRP), is an effective treatment for periodontitis.

Click here for the full text online article.

_______________________________________________________

Schaudinn C, Gorur A, Keller D, Sedghizadeh PP, Costerton JW. Center for Biofilms, School of Dentistry, University of Southern California, Los Angeles, CA90089, USA. Periodontitis: An archetypical biofilm disease. J Am Dent Assoc. 2009 Aug;140(8):978-86.

BACKGROUND: Periodontitis is a classic example of biofilm-mediated diseases.

METHODS: The authors reviewed selected publications in English-language peer-reviewed journals with respect to microbial biofilms, focusing on representative works that provided a historical to a contemporary perspective on periodontal oral biofilms in the larger context of biofilm microbiology.

RESULTS: Developments in advanced microscopy and molecular microbiology have allowed scientists to examine and characterize microbial biofilm-mediated diseases, such as periodontitis, more accurately than in the past.

CONCLUSIONS: Periodontitis, like other biofilm infections, is refractory to antibiotic agents and host defenses because the causative microbes live in complex communities that persist despite challenges that range from targeted antibiotic agents to phagocytosis.

CLINICAL IMPLICATIONS: The regular delivery of nontargeted antibiofilm agents may be an effective strategy for treating biofilms, especially if these agents include oxidative agents that dissolve the biofilm matrix.

_______________________________________________________

Preliminary Data on Periodontal Disease Treatment Using Topical Oxidizing Agents - abstract link

1151 Preliminary Data on Periodontal Disease Treatment Using Topical Oxidizing Agents DC Keller DMD1, LT Nguyen, BS2, LR Jobe, BS2, and BJ Sindelar PT, PhD2 1Perio Protect LLC, Saint Louis, MO; 2School of Physical Therapy, Ohio University, Athens, OH

Click here for the research poster presentation.

_______________________________________________________

SEM Results of Periopathogenic Control with the Perio Protect Method - abstract link

1186 SEM Results of Periopathogenic Control with the Perio Protect Method D.C. KELLER 1, B. COSTERTON 2, C. SCHAUDINN 2, and G.S. KELLER 3, 1Perio Protect, Saint Louis, MO, USA, 2USC School of Dentistry, Los Angeles, CA, USA, 3Keller Professional Group P.C, St. Louis, MO, USA


Above are Before treatment (left) and after 17 days of Perio Protect treatment (right), both scales represent 5 μm.

Click here for the research poster presentation.

_______________________________________________________

C-reactive protein changes during Perio Protect treatment of periodontal disease - abstract link

1195 C-reactive protein changes during Perio Protect treatment of periodontal disease C. STEELE, Keller Professional Group PC, St. Louis, MO, USA, B.J. SINDELAR, Ohio University, Athens, USA, and D.C. KELLER, Perio Protect, Saint Louis, MO, USA

Click here for the research poster presentation.

_______________________________________________________

Initial Study of the Perio Protect TM Treatment for Periodontal Disease - abstract link

1164 Initial Study of the Perio Protect TM Treatment for Periodontal Disease L.E. WENTZ 1, A.M. BLAKE 1, D.C. KELLER 2, and B.J. SINDELAR 2, 1Ohio University, Athens, USA, 2Keller Professional Group PC, St. Louis, MO, USA

Click here for the research poster presentation.

• “About 66% of Americans 35–44 years old in this study were reported to have had periodontitis or advanced periodontitis” (5mm pockets or >)

Position Paper.
Epidemiology of Periodontal Diseases*
J Periodontol1996;67:935-945.

• “5% to 20% of any population suffers from severe generalized periodontitis, even though moderate disease affects a majority of adults.”
• “If the disease is defined as the identification of at least one site with clinical attachment loss (CAL) of 2 mm or more, around 80% of all adults are affected, and over 90% of those aged 55 to 64.8 “
• “When the case-definition is at least one site with CAL of 4 mm or more, the prevalence in those aged 55 to 64 drops to 64%.”

• THIS PAPER WAS PREPARED BY THE RESEARCH, Science, and Therapy Committee of The American Academy of Periodontology and is intended for the information of the dental profession.

Beirne P et al.
Routine scale and polish for periodontal health in adults.
Cochrane Database Syst Rev. 2005 Jan. 25 (1).

Jorgensen MG et al.
Periodontal antimicrobials – finding the right solutions.
Int Dent J 2005 Feb 55 (1) 3-12.

BOTH DOCUMENT THE FOLLOWING
• A combination of brushing interdental cleaning and chemotherapeutic agents are beneficial in managing periodontal disease.

Dorfer CE.
Antimicrobials for the treatment of aggressive periodontitis.
Oral Diseases 2003, 9 (suppl. 1), 51-53.

• In recent publications (Slots and Jorgensen, 2002, Slots and Ting 2002, Walker and Karpinia, 2002) the use of antimicrobials as an adjunct to mechanical therapy has been regarded as beneficial to improve the therapeutic outcome.

Ishikawa I, Baehni.
Non-surgical periodontal therapy – where do we stand now.
Periodontol (36) 2004;);9-13.

No single antibiotic is effective in controlling periodontal disease. Rather a combination with scaling and root planing has proven most effective.

• Metronidazole / amoxycillin + S & RP
• Doxycycline
• Minocycline
• Chlorhexidine
• Povidone-iodine

Shiloah J, Patters MR, Dean JW 3rd, Bland P, Toledo G.
The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus in humans 1 year after 4 randomized treatment modalities.
J Periodontol. 1998 Dec;69(12):1364-72.

1) scaling and root planing; 2) pocket reduction through osseous surgery and apically-positioned flap; 3) modified Widman flap; and 4) modified Widman flap and topical application of saturated citric acid at pH 1 for 3 minutes.
• Patients rinsed with 0.12% chlorhexidine for the first 3 months postoperatively and received a prophylaxis every 3 months.
• The choice of treatment modality did not affect the prevalence of the target species at 1 year post-treatment. These results suggest that prevalence of microbial pathogens negatively affects the 1 year outcome of periodontal surgical and nonsurgical therapy.

Killoy WJ.
Local delivery of antimicrobials: a new era in the treatment of adult periodontitis.
Compend Contin Educ Dent. 1999;20(4 Suppl):13-8; quiz 34-5.

• This article discusses the principles, products, and techniques currently available for local delivery of antimicrobials in the treatment of adult periodontitis. Four principles provide the scientific basis for the treatment of periodontitis: it is caused by bacteria; it cannot be cured, but it can be controlled; clinicians cannot remove all the plaque and calculus; and periodontitis re-infects. This article stresses how the local delivery of antimicrobials can help the clinician achieve the goals of arresting the disease and maintaining the disease in the arrested or controlled state. Rationales for reevaluating the treated patient and treatment options are presented. Local-delivery systems are reviewed, stressing those available in the United States. Pharmacokinetics, multi-center randomized trials, and techniques are presented.

Marshall MV, Cancro LP, Fischman SL.
Hydrogen peroxide: a review of its use in dentistry.
J Periodontol. 1995 Sep;66(9):786-96.

• Hydrogen peroxide has been used in dentistry alone or in combination with salts for over 70 years. Studies in which 3% H2O2 or less were used daily for up to 6 years showed occasional transitory irritant effects only in a small number of subjects with preexisting ulceration, or when high levels of salt solutions were concurrently administered. This (and later) studies have shown that at 3% or less, no cocarcinogenic activity or adverse effects were observed in the hamster cheek pouch following lengthy exposure to H2O2. In patients, prolonged use of hydrogen peroxide decreased plaque and gingivitis indices. However, therapeutic delivery of H2O2 to prevent periodontal disease required mechanical access to subgingival pockets. Furthermore, wound healing following gingival surgery was enhanced due to the antimicrobial effects of topically administered hydrogen peroxide.

Katsuragi H, Ohtake M, Kurasawa I, Saito K.
Intracellular production and extracellular release of oxygen radicals by PMNs and oxidative stress on PMNs during phagocytosis of periodontopathic bacteria.
Odontology. 2003 Sep;91(1):13-8.

• Both the intracellular and extracellular oxygen radical production by PMNs phagocytosing F. nucleatum was significantly greater than that of PMNs phagocytosing P. gingivalis and A. actinomycetemcomitans ( P < 0.01 by the Mann-Whitney test). Moreover, after 4 h of incubation, the oxidative stress of PMNs phagocytosing F. nucleatum was significantly greater than that of PMNs phagocytosing P. gingivalis and A. actinomycetemcomitans. We conclude that a high level of superoxide production by PMNs may damage not only periodontopathic bacteria but also PMNs themselves, and may be correlated with the destruction of periodontal tissue.

Firatli E, Unal T, Onan U, Sandalli P.
J Clin Periodontol. 1994 Nov;21(10):680-3.
Antioxidative activities of some chemotherapeutics. A possible mechanism in reducing gingival inflammation.

• Inflammatory periodontal diseases are related to dental plaque formation. Increase in the perfusion of the inflamed tissue results in increased oxygen supply. Although oxygen has healing effects, it is bound to be a mediator of peroxidation in biological membranes. Chemotherapeutic agents such as chlorhexidine, listerine, sanguinarine, and cetylpridinium chloride and oral antibiotics such as tetracycline HCl and doxycyline were tested for their antioxidative activities. While doxycycline has the highest antioxidant activity in lower volumes (0.1 ml), sanguinarine, listerine and a pace after them, tetracycline HCl, had similar effects in higher volumes (0.3 and 0.4 ml). The results showed that in addition to their antiseptic or antimicrobial effects, these preparations have an antioxidative activity against spontaneous oxidation.

Bezerra MM, Brito GA, Ribeiro RA, Rocha FA.
Low-dose doxycycline prevents inflammatory bone resorption in rats.
Braz J Med Biol Res. 2002 May;35(5):613-6.

• Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation
• Doxycycline (DX) (< or =10 mg kg-1 day-1), is a known MMP inhibitor
• The data show that doxycycline inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties.

Donahue HJ, Iijima K, Goligorsky MS, Rubin CT, Rifkin BR.
Regulation of cytoplasmic calcium concentration in tetracycline-treated osteoclasts.
J Bone Miner Res. 1992 Nov;7(11):1313-8.

• Tetracyclines can enter the osteoclast and bind calcium.
• Tetracycline pretreatment significantly decreased the cytosolic Ca2+ response to extracellular CaCl2.
• Tetracyclines have a specific effect on extracellular Ca(++)-stimulated cytosolic Ca2+ mobilization in osteoclasts.
• Tetracyclines trigger an attenuated signal response associated with decreased osteoclastic resorption.

Holmes SG, Still K, Buttle DJ, Bishop NJ, Grabowski PS.
Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors.
Bone. 2004 Aug;35(2):471-8.

• Osteoclast formation over 20 days was completely abrogated when tetracycline derivatives doxycycline and minocycline (concentration of 250 ng/ml) were included in cell cultures.
• The exact mechanism of tetracycline action is not known.

Mulari MT, Qu Q, Harkonen PL, Vaananen HK.
Osteoblast-like cells complete osteoclastic bone resorption and form new mineralized bone matrix in vitro.
Calcif Tissue Int. 2004 Sep;75(3):253-61.

• Osteoblast-like cells, not macrophages, remove the remaining organic materials. After cleaning the lacuna, osteoblast-like cells deposit new collagen fibrils and calcify the newly formed matrix as visualized by tetracycline accumulation.