Effect of Three Periodontal Therapies in Current Smokers and Non-Smokers

NCT ID: NCT00066066

Last Updated: 2013-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2009-07-31

Brief Summary

The purpose of this study is to determine in current and non-smokers the clinical and microbiological effects of 3 therapies: scaling and root planing (SRP) alone; SRP in combination with the orally administered antibiotic metronidazole; and SRP with the orally administered antibiotics metronidazole and amoxicillin along with the locally delivered antibiotic doxycycline at periodontal pockets >= 4 mm.

Detailed Description

Cigarette smokers have more severe periodontal disease and more widespread colonization by periodontal pathogens than non smokers. In addition, smokers respond less well to periodontal therapies, particularly mechanical therapies such as scaling and root planing (SRP) and surgery. Recent data from our laboratory have indicated that treatment that included antibiotics produced a better clinical effect in smokers than mechanical therapy alone. Thus, the purpose of the present investigation is to compare the immediate and long-term effects of 3 periodontal therapies on clinical, microbiological and host parameters in current and non smokers. In this double blind, placebo-controlled, randomized study, 108 current smokers and 108 non smokers will be randomly assigned to 1 of 3 treatment groups: SRP alone; SRP + systemically administered metronidazole; SRP + systemically administered amoxicillin and metronidazole and local delivery of doxycycline at pockets > 4 mm. Plaque Index, Gingival Index, % of sites with bleeding on probing, suppuration, pocket depth and attachment level will be measured at 6 sites per tooth at all teeth excluding 3rd molars at baseline, 3, 6, 12, 18 and 24 months. Subgingival plaque samples taken from the mesial aspect of each tooth at the same time points will be analyzed individually for their content of 40 subgingival species using checkerboard DNA-DNA hybridization. Antibody levels to 20 subgingival species will be measured in serum samples taken at baseline, 6 and 24 months. Levels of IL-1b, IL-10 and IFNg will be measured in GCF samples taken from the 4 deepest pockets at baseline, 3, 6 and 24 months. The major hypothesis to be tested is whether smokers respond better to periodontal therapies that include 1 or more antibiotics. Other hypotheses will test whether host and microbiological parameters differ between smokers and non smokers and if such parameters are comparably altered after therapy in both groups. The results will be of immediate clinical benefit to the large segment of periodontal patients who smoke cigarettes. Smokers make up 26 - 30% of the adult population and form a disproportionately high segment of the population requiring periodontal treatment. They may have special needs in terms of periodontal therapy which should be clarified by the proposed investigation. In addition, the cigarette smoker is an example of a periodontal patient who is "compromised" in terms of his/her ability to cope with infectious diseases. The proposed investigation should provide a model to examine methods that could be useful in treating compromised patients whether compromised by harmful habits such as smoking, systemic disease or genetic background.

Conditions

Periodontitis; Periodontal Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Scaling and root planing alone

Full mouth scaling and root planing (SRP) alone plus a placebo pill taken twice daily for 2 weeks.

Group Type: PLACEBO_COMPARATOR

Scaling and root planing

Intervention Type: PROCEDURE

Scaling and root planning (SRP) is the mechanical debridement of the tooth and root surfaces and is standard of care in periodontal therapy.

SRP + Metronidazole

Full mouth Scaling and Root Planing plus Metronidazole (MET) 250 mg tid x 14 days

Group Type: ACTIVE_COMPARATOR

Metronidazole

Intervention Type: DRUG

Metronidazole (MET) is an antibiotic that is particularly effective against Gram negative bacterial species. The dose for this study is: 250 mg tid x 14d.

SRP + MET + Amoxicillin + Doxycycline

Full mouth Scaling and Root Planing plus Metronidazole (MET) 250 mg tid x 14 d and Amoxicillin (AMOX) 500 mg tid for 14 days and local drug delivery of Doxycycline (TET LDD) in pockets \>4mm

Group Type: ACTIVE_COMPARATOR

Amoxicillin

Intervention Type: DRUG

Amoxicillin (AMOX) is a broad spectrum antibiotic and was prescribed at 500 mg tid for 14d.

Doxycycline

Intervention Type: DRUG

The ATRIDOX (doxycycline hyclate) ® product is a subgingival controlled-release product composed of a two syringe mixing system. Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable polymeric formulation composed of 36.7% poly(DLlactide) (PLA) dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains 50 mg of doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of doxycycline hyclate. Upon contact with the crevicular fluid, the liquid product solidifies and then allows for controlled release of drug for a period of 7 days. Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline.

Interventions

Scaling and root planing

Scaling and root planning (SRP) is the mechanical debridement of the tooth and root surfaces and is standard of care in periodontal therapy.

Intervention Type: PROCEDURE

Metronidazole

Metronidazole (MET) is an antibiotic that is particularly effective against Gram negative bacterial species. The dose for this study is: 250 mg tid x 14d.

Intervention Type: DRUG

Amoxicillin

Amoxicillin (AMOX) is a broad spectrum antibiotic and was prescribed at 500 mg tid for 14d.

Intervention Type: DRUG

Doxycycline

The ATRIDOX (doxycycline hyclate) ® product is a subgingival controlled-release product composed of a two syringe mixing system. Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable polymeric formulation composed of 36.7% poly(DLlactide) (PLA) dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains 50 mg of doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of doxycycline hyclate. Upon contact with the crevicular fluid, the liquid product solidifies and then allows for controlled release of drug for a period of 7 days. Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline.

Intervention Type: DRUG

Other Intervention Names

Atridox

Eligibility Criteria

Inclusion Criteria

• > 20 teeth
• > 5% sites (approx. 8 sites) with pocket depth > 4 mm and / or 5% sites with attachment level > 4 mm and mean AL < 4.5 mm and mean PD < 3.9 mm (not including tooth brush abrasions).

Exclusion Criteria

• > 50% of sites with pocket depth or attachment level > 4 mm
• Pregnancy or nursing
• Periodontal or antibiotic therapy in the previous 6 months
• Any systemic condition which might influence the course of periodontal disease or treatment (e.g. diabetes, AIDS)
• Any systemic condition which requires antibiotic coverage for routine periodontal procedures (e.g. heart conditions, joint replacements etc.)
• Liver disease
• Any known allergy to amoxicillin, metronidazole or doxycycline
• Lactose intolerance

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Dental and Craniofacial Research (NIDCR)

NIH

Sponsor Role: collaborator

The Forsyth Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Haffajee, DDS

Role: PRINCIPAL_INVESTIGATOR

Boston, MA

Ricardo Teles, DDS, DMSc

Role: PRINCIPAL_INVESTIGATOR

The Forsyth Institute

Locations

Department of Periodontology

Cambridge, Massachusetts, United States

Countries

United States

References

Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database Syst Rev. 2020 Nov 16;11(11):CD012568. doi: 10.1002/14651858.CD012568.pub2.

Reference Type: DERIVED

PMID: 33197289 (View on PubMed)

Other Identifiers

R01DE014242

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIDCR-14242

Identifier Type: -

Identifier Source: org_study_id