Mechanisms and Treatment Response of Aggressive Periodontitis in Children

Aggressive Periodontitis Clinical Trial

Official title:

Mechanisms and Treatment Response of Aggressive Periodontitis in Children: Aberrant Immunological Phenotypes/Functions in the Progression of AgP

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01330719
• Other study ID #: IRB201400349-N
• Secondary ID: R01DE019456
• Status: Completed
• Phase: N/A
• Start date: December 2006
• Est. completion date: December 2, 2022

Study information

• Verified date: March 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although of low prevalence, aggressive periodontitis is a rapid destructive form of periodontal disease that initiates at a young age, leading to premature loss of first molars and incisors. Little is known on the mechanisms of this disease. It is imperative to understand mechanisms of disease to establish proper treatment. We have established a controlled study in a comparable population presenting similar aggressive disease characteristics to evaluate the mechanisms of this disease. It is the goal of this study to determine immunological and microbiological mechanisms responsible for the rapid tissue destruction in children with localized aggressive periodontitis and how traditional periodontal intervention affects these mechanisms. Important knowledge gained with this proposal will aid in defining specific treatment approaches to better control disease progression and prevent disease initiation in susceptible individuals.

Description:

There a multiple appointments throughout the study which can vary depending upon if a patient has the disease present or not.

If the patient has gum disease: At the initial examination, some samples will be collected:

the natural fluid that comes from the gums and the bacteria that are present there will be collected by inserting a piece of paper and a filter strip in the spaces between teeth and gums; blood samples may also be taken by a phlebotomist to evaluate some inflammatory signs of disease and possible genetic markers (about 5 teaspoons at each visit); and a cheek swab may be taken by gently rubbing a little brush into the inside of the cheeks. Patients also may be asked to spit into a container we provide. Tissues from gums that are usually discarded may also be collected during treatment. When patients return for re-evaluation of their gums, all these samples may be collected again at 3, 6, 12, 18 and 24 months after the initial therapy. After 24 months, only clinical examinations may be performed, up to 3 more visits within the following 3 years.

If the patient does not have gum disease: If gums are healthy and the patient does not need treatment, they will be seen every 6 months for examination and cleanings, then sample collections may also be taken at these visits up to 24 months. These sample collections are done to be studied by genetic tests, which will tell us if there are specific genetic markers (inherited markers) associated with this disease, and also other laboratory testing, which will help the researchers identify how the body responds to bacteria. These markers will also be evaluated in family members (parents, grandparents or siblings), when possible, to check for the likelihood of these members developing this disease.

Regardless of the patient's gum condition, investigators will also evaluate current and past dental x-rays to determine if there were signs of this disease in the past.

Investigators may also take photos of the teeth and gums.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 514
• Est. completion date: December 2, 2022
• Est. primary completion date: May 29, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 90 Years

Eligibility

Inclusion child/adolescent:

• Male or female, aged 5 to 25

• In good general health as evidenced by medical history

• Diagnosed with localized aggressive periodontitis (LAP), defined by the presence of attachment loss = 2mm and detected bone loss on at least two sites, involving first molars and/or incisors, or

• Periodontally healthy (defined by absence of clinical signs of periodontitis) related or not to LAP participants

Inclusion parent /grandparent:

• Male or female, up to age 90 years

• Parent or grandparent of an enrolled participant with LAP

Exclusion child/adolescent:

• Diagnosed with any systemic diseases or conditions that could influence the progression and/or clinical characteristics of periodontal disease (i.e., immunosuppression, diabetes, neutropenia or blood disorders).

• Patients that have taken antibiotics within the last 3 months* or require antibiotic prophylaxis prior to initial visit.

• Patients that are currently taking medications that could influence the characteristics or response to periodontal treatment (example: immune-suppressive drugs, such as cyclosporine or steroids).

• Smokers (=10 cigarettes a day for over 6 months)

• Pregnant/lactating women as pregnancy causes gingival changes that could confound study results.

• Any psychiatric conditions that will inhibit participants from proper understanding of study procedures as determined by the PI/clinician investigator.

• Patients may still enroll but will be scheduled for initial visit 3 months later

Exclusion parent/grandparent:

• Patients that have taken antibiotics within the last 3 months* or require antibiotic prophylaxis prior to initial visit.

• Pregnant/lactating women as pregnancy causes gingival changes that could confound study results.

• Any psychiatric conditions that will inhibit participants from proper understanding of study procedures as determined by the PI/clinician investigator.

Related Conditions & MeSH terms

• Aggression
• Aggressive Periodontitis
• Periodontitis

Intervention

Procedure:
• Diseased periodontal treatment
Treatment includes scaling and root planing with systemic antibiotics, Amoxicillin 500 mg and Metronidazole 250 mg tid 7 days. At certain intervals after the scaling and root planing, your gums will be reevaluated. You will receive further surgical gum therapy only if your gums haven't shown improvement after first treatment on the reevaluation appointments. If surgery is needed, a bone substituting material may be necessary to "fill" the spaces where bone has been destroyed by the disease. Extraction of teeth might also be part of gum treatment if the disease is very severe. Re-treatment with antibiotics also may be necessary depending on the response after treatment. You are usually re-examined and receive additional cleanings every 3 to 6 months to ensure the disease does not come back.
• Conventional periodontal treatment
Scaling and gum measurement will be taken to compare to the treated group.- If it is determined that you do not have this disease, a conventional cleaning is done, usually every 6 months. This is all part of normal clinical care.

Locations

Country	Name	City	State
United States	Acorn Dental Clinic	Brooker	Florida
United States	Broward College	Fort Lauderdale	Florida
United States	Azalea Dental Clinic	Gainesville	Florida
United States	Dental Clinical Research Unit, University of Florida	Gainesville	Florida
United States	UF Hialeah Dental Clinic	Hialeah	Florida
United States	Duval County Department of Health	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	UF Naples Pediatric Dental Clinic	Naples	Florida
United States	Gadsden County Health Department--Quincy Dental Clinic	Quincy	Florida
United States	Leon County Health Department	Tallahassee	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	National Institute of Dental and Craniofacial Research (NIDCR)

Country where clinical trial is conducted

United States, 

References & Publications (15)

Agarwal S, Suzuki JB, Riccelli AE. Role of cytokines in the modulation of neutrophil chemotaxis in localized juvenile periodontitis. J Periodontal Res. 1994 Mar;29(2):127-37. doi: 10.1111/j.1600-0765.1994.tb01101.x. — View Citation

Albandar JM, Tinoco EM. Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000. 2002;29:153-76. doi: 10.1034/j.1600-0757.2002.290108.x. No abstract available. — View Citation

Albandar JM. Epidemiology and risk factors of periodontal diseases. Dent Clin North Am. 2005 Jul;49(3):517-32, v-vi. doi: 10.1016/j.cden.2005.03.003. — View Citation

Albandar JM. Juvenile periodontitis--pattern of progression and relationship to clinical periodontal parameters. Community Dent Oral Epidemiol. 1993 Aug;21(4):185-9. doi: 10.1111/j.1600-0528.1993.tb00753.x. — View Citation

Alfant B, Shaddox LM, Tobler J, Magnusson I, Aukhil I, Walker C. Matrix metalloproteinase levels in children with aggressive periodontitis. J Periodontol. 2008 May;79(5):819-26. doi: 10.1902/jop.2008.070513. — View Citation

Beliveau D, Magnusson I, Bidwell JA, Zapert EF, Aukhil I, Wallet SM, Shaddox LM. Benefits of early systemic antibiotics in localized aggressive periodontitis: a retrospective study. J Clin Periodontol. 2012 Nov;39(11):1075-81. doi: 10.1111/jcpe.12001. Epu — View Citation

Christersson LA, Slots J, Rosling BG, Genco RJ. Microbiological and clinical effects of surgical treatment of localized juvenile periodontitis. J Clin Periodontol. 1985 Jul;12(6):465-76. doi: 10.1111/j.1600-051x.1985.tb01382.x. — View Citation

Goncalves PF, Huang H, McAninley S, Alfant B, Harrison P, Aukhil I, Walker C, Shaddox LM. Periodontal treatment reduces matrix metalloproteinase levels in localized aggressive periodontitis. J Periodontol. 2013 Dec;84(12):1801-8. doi: 10.1902/jop.2013.130 — View Citation

Koutouzis T, Haber D, Shaddox L, Aukhil I, Wallet SM. Autoreactivity of serum immunoglobulin to periodontal tissue components: a pilot study. J Periodontol. 2009 Apr;80(4):625-33. doi: 10.1902/jop.2009.080422. — View Citation

Page RC, Baab DA. A new look at the etiology and pathogenesis of early-onset periodontitis. Cementopathia revisited. J Periodontol. 1985 Dec;56(12):748-51. doi: 10.1902/jop.1985.56.12.748. — View Citation

Shaddox L, Wiedey J, Bimstein E, Magnuson I, Clare-Salzler M, Aukhil I, Wallet SM. Hyper-responsive phenotype in localized aggressive periodontitis. J Dent Res. 2010 Feb;89(2):143-8. doi: 10.1177/0022034509353397. Epub 2009 Dec 30. — View Citation

Shaddox LM, Huang H, Lin T, Hou W, Harrison PL, Aukhil I, Walker CB, Klepac-Ceraj V, Paster BJ. Microbiological characterization in children with aggressive periodontitis. J Dent Res. 2012 Oct;91(10):927-33. doi: 10.1177/0022034512456039. Epub 2012 Aug 3. — View Citation

Shaddox LM, Wiedey J, Calderon NL, Magnusson I, Bimstein E, Bidwell JA, Zapert EF, Aukhil I, Wallet SM. Local inflammatory markers and systemic endotoxin in aggressive periodontitis. J Dent Res. 2011 Sep;90(9):1140-4. doi: 10.1177/0022034511413928. Epub 2 — View Citation

Sweeney EA, Alcoforado GA, Nyman S, Slots J. Prevalence and microbiology of localized prepubertal periodontitis. Oral Microbiol Immunol. 1987 Jun;2(2):65-70. doi: 10.1111/j.1399-302x.1987.tb00292.x. — View Citation

Zambon JJ, Christersson LA, Slots J. Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotypes within families. J Periodontol. 1983 Dec;54(12):707-11. doi: 10.1902/jop.1983.54.12.707. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SNPs and DNA methylation	The investigators are doing analysis of single nucleotide polymorphisms (DNA sequence variation) and methylation (addition of a methyl group) of DNA of specific genes related to inflammation.	24 months
Secondary	Systemic inflammatory levels	The investigators are testing for systemic (plasma levels) and local (gingival fluid levels) markers of inflammation.	24 months