Metronidazole and Amoxicillin for the Treatment of Type 2 Diabetic Subjects With Periodontitis

Study Overview
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Brief Summary
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Diabetes mellitus (DM) is a widely prevalent disease associated with several major systemic and oral complications, such as periodontitis. The use of adjunctive local and/or systemic antimicrobials has been proposed to improve the clinical and glycemic outcomes of the scaling and root planing (SRP) in diabetic subjects. The combination of metronidazole (MTZ) and amoxicillin (AMX) has been largely recognized as an effective therapy for improving the clinical and microbiological outcomes of SRP in the treatment of with chronic periodontitis (ChP). However, no previous clinical trials to date have evaluated the effects of this antibiotic combination in the treatment of diabetic subjects with periodontitis. Therefore, the aim of this randomized clinical trial (RCT) will be to evaluate the clinical and microbiological effects of the use of MTZ+AMX as adjuncts to SRP for the treatment of type 2 diabetic subjects with generalized ChP.

Official Title
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Metronidazole and Amoxicillin as Adjuncts to Scaling and Root Planing for the Treatment of Type 2 Diabetic Subjects With Periodontitis: a Randomized Placebo-controlled Clinical Trial

Conditions
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Periodontitis

Intervention / Treatment
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* Procedure: SRP
* Other: Placebo
* Drug: MTZ+AMX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 35 years of age Diagnosis of type 2 DM for ≥ 5 years DM treatment with diet and insulin supplementation or oral hypoglycemic agents Glycated hemoglobin (HbA1c) levels ≥ 6.5% ≤ 11% At least 15 teeth More than 30% of the sites with probing depth (PD) and clinical attachment level (CAL) ≥ 4 mm Minimum of six teeth with at least one site with PD and CAL ≥ 5 mm and bleeding on probing (BoP) at baseline. Exclusion Criteria: Pregnancy Lactation Current smoking Smoking within the past 5 years Scaling and root planing (SRP) in the previous 12 months Antimicrobial therapies during the previous 6 months Medical conditions requiring prophylactic antibiotic coverage Continuous use of mouthrinses containing antimicrobials in the preceding 3 months Systemic conditions (except DM) that could affect the progression of periodontitis (e.g. immunological disorders, osteoporosis) Long-term administration of anti-inflammatory Long-term administration of immunosuppressive medications Allergy to metronidazole and/or amoxicillin Presence of periapical pathology Use of orthodontic appliances Presence of extensive prosthetic rehabilitation Major complications of DM (i.e. cardiovascular and peripheral vascular diseases [ulcers, gangrene and amputation], neuropathy and nephropathy)

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SRP+MTZ+AMX<br>Scaling and root planing (SRP) + metronidazole (MTZ; 400 mg thrice a day [TID] for 14 days) + amoxicillin (AMX; 500 mg TID for 14 days) | Procedure: SRP<br>* SRP in four to six appointments lasting approximately 1 h each, using manual curettes and ultrasonic device under local anesthesia.<br>Drug: MTZ+AMX<br>* Administration of antibiotics (metronidazole and amoxicillin) for 14 days started immediately after the first session of SRP.<br>|
| Placebo Comparator: SRP+placebo<br>Scaling and root planing + placebo | Procedure: SRP<br>* SRP in four to six appointments lasting approximately 1 h each, using manual curettes and ultrasonic device under local anesthesia.<br>Other: Placebo<br>* Administration of placebo for 14 days started immediately after the first session of SRP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in number of sites with probing depth (PD) ≥5 mm post-treatment |  | From baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD and clinical attachment level (CAL) changes at initially moderate sites |  | From baseline to 12 months and from baseline to 24 months | 
| PD and CAL changes at initially deep sites |  | From baseline to 12 months and from baseline to 24 months | 
| Changes in number of sites with PD ≥5mm |  | From baseline to 12 months and from baseline to 24 months | 
| Full-mouth PD and CAL |  | Baseline, 3, 6, 12 and 24 months | 
| Full-mouth percentages of sites with plaque |  | Baseline, 3, 6, 12 and 24 months | 
| Full-mouth percentages of sites with marginal bleeding |  | Baseline, 3, 6, 12 and 24 months | 
| Full-mouth percentages of sites with bleeding on probing |  | Baseline, 3, 6, 12 and 24 months | 
| Full-mouth percentages of sites with suppuration |  | Baseline, 3, 6, 12 and 24 months | 
| Full-mouth percentages of sites with PD ≥5mm |  | Baseline, 3, 6,12 and 24 months | 
| Serum levels of glycated hemoglobin (HbA1c) |  | Baseline, 3, 6, 12 and 24 months | 
| Serum levels of fasting plasma glucose FPG |  | Baseline, 3, 6, 12 and 24 months | 
| Levels of periodontal pathogenic bacterial species |  | Baseline, 3, 6, 12 and 24 months | 
| Occurrence of adverse events |  | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontitis, Diabetes