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

• ClinicalTrials.gov Identifier: NCT00066066
• Recruitment Status: Completed
• First Posted: August 5, 2003
• Results First Posted: April 22, 2013
• Last Update Posted: April 22, 2013
• Sponsor: The Forsyth Institute
• Collaborator: National Institute of Dental and Craniofacial Research (NIDCR)
• Information provided by (Responsible Party): The Forsyth Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Periodontitis; Periodontal Diseases	Procedure: Scaling and root planing; Drug: Metronidazole; Drug: Amoxicillin; Drug: Doxycycline	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Three Periodontal Therapies in Current Smokers and Non-Smokers
• Study Start Date: July 2003
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Scaling and root planing alone; Full mouth scaling and root planing (SRP) alone plus a placebo pill taken twice daily for 2 weeks.	Procedure: 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.
Active Comparator: SRP + Metronidazole; Full mouth Scaling and Root Planing plus Metronidazole (MET) 250 mg tid x 14 days	Drug: 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.
Active Comparator: 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	Drug: Amoxicillin; Amoxicillin (AMOX) is a broad spectrum antibiotic and was prescribed at 500 mg tid for 14d.; 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.; Other Name: Atridox

Outcome Measures

Primary Outcome Measures :

1. Change in Mean Clinical Attachment Level. [ Time Frame: Baseline, 3, 6 and 12 months ]
   Periodontal diseases are clinically diagnosed by assessments of gingival inflammation and measurements of tissue destruction. The damage to the apparatus of support of the teeth is quantified using measurements of probing pocket depth (PD) and clinical attachment level (CAL). These measurements are obtained using a periodontal probe which is introduced into the gingival sulcus to determine the distance in millimeters from the gingival margin to the depth of the sulcus or pocket (PD). Since the gingival margin fluctuates in response to inflammation (hyperplasia) or might recede, a more accurate measure of loss of attachment is obtained using the CAL, which measures the distance from a "fixed" landmark on the tooth such as the cemento-enamel junction to the depth of the pocket. Changes in CAL from baseline were used to assess results obtained with the treatment of periodontal diseases.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Department of Periodontology

Cambridge, Massachusetts, United States, 02142

Sponsors and Collaborators

The Forsyth Institute

National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Principal Investigator: Anne Haffajee, DDS; Boston, MA
• Principal Investigator: Ricardo Teles, DDS, DMSc; The Forsyth Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD012568. doi: 10.1002/14651858.CD012568.pub2.

• Responsible Party: The Forsyth Institute
• ClinicalTrials.gov Identifier: NCT00066066
• Other Study ID Numbers: NIDCR-14242; R01DE014242 ( U.S. NIH Grant/Contract )
• First Posted: August 5, 2003
• Results First Posted: April 22, 2013
• Last Update Posted: April 22, 2013
• Last Verified: March 2013

Additional relevant MeSH terms:

Periodontitis; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Amoxicillin; Metronidazole; Doxycycline; Anti-Bacterial Agents; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials