Clinical trial NCT02135952: Metronidazole and Amoxicillin for the Treatment of Type 2 Diabetic Subjects With Periodontitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Periodontitis
Keywords: Periodontitis
Diabetes
Lead sponsor: University of Guarulhos
Sponsor class: OTHER
First posted: 2014-05-12
Enrollment: 58
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Changes in number of sites with probing depth (PD) ≥5 mm post-treatment
timeFrame: From baseline to 12 months
Secondary outcomes:
measure: PD and clinical attachment level (CAL) changes at initially moderate sites
timeFrame: From baseline to 12 months and from baseline to 24 months
measure: PD and CAL changes at initially deep sites
timeFrame: From baseline to 12 months and from baseline to 24 months
measure: Changes in number of sites with PD ≥5mm
timeFrame: From baseline to 12 months and from baseline to 24 months
measure: Full-mouth PD and CAL
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Full-mouth percentages of sites with plaque
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Full-mouth percentages of sites with marginal bleeding
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Full-mouth percentages of sites with bleeding on probing
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Full-mouth percentages of sites with suppuration
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Full-mouth percentages of sites with PD ≥5mm
timeFrame: Baseline, 3, 6,12 and 24 months
measure: Serum levels of glycated hemoglobin (HbA1c)
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Serum levels of fasting plasma glucose FPG
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Levels of periodontal pathogenic bacterial species
timeFrame: Baseline, 3, 6, 12 and 24 months
measure: Occurrence of adverse events
timeFrame: 14 days
Other outcomes:
Locations:
city: Guarulhos
country: Brazil
facility: University of Guarulhos
state: São Paulo
Study officials:
affiliation: University of Guarulhos
name: Poliana M Duarte, PhG
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amid R, Tabeie MB, Kadkhodazadeh M, Mehdizadeh AR, Youssefi N. Local concentration of systemic amoxicillin and metronidazole in healthy and inflamed gingiva: a comparative in vivo study. Drug Metabol Drug Interact. 2012 May 10;27(2):113-8. doi: 10.1515/dmdi-2012-0003.
citation: Borgnakke WS, Ylostalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Clin Periodontol. 2013 Apr;40 Suppl 14:S135-52. doi: 10.1111/jcpe.12080.
citation: Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol. 2009 Mar;80(3):364-71. doi: 10.1902/jop.2009.080540.
citation: Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Microbiologic testing and outcomes of full-mouth scaling and root planing with or without amoxicillin/metronidazole in chronic periodontitis. J Periodontol. 2010 Jan;81(1):15-23. doi: 10.1902/jop.2009.090390.
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citation: Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Dec;39(12):1149-58. doi: 10.1111/jcpe.12004. Epub 2012 Sep 27.
citation: Grossi SG, Skrepcinski FB, DeCaro T, Robertson DC, Ho AW, Dunford RG, Genco RJ. Treatment of periodontal disease in diabetics reduces glycated hemoglobin. J Periodontol. 1997 Aug;68(8):713-9. doi: 10.1902/jop.1997.68.8.713.
citation: Jimenez M, Hu FB, Marino M, Li Y, Joshipura KJ. Type 2 diabetes mellitus and 20 year incidence of periodontitis and tooth loss. Diabetes Res Clin Pract. 2012 Dec;98(3):494-500. doi: 10.1016/j.diabres.2012.09.039. Epub 2012 Oct 3.
citation: Lang NP, Tonetti MS. Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent. 2003;1(1):7-16.
citation: Silva MP, Feres M, Sirotto TA, Soares GM, Mendes JA, Faveri M, Figueiredo LC. Clinical and microbiological benefits of metronidazole alone or with amoxicillin as adjuncts in the treatment of chronic periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2011 Sep;38(9):828-37. doi: 10.1111/j.1600-051X.2011.01763.x. Epub 2011 Jul 15.
citation: Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA. The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol. 2013 Mar;84(3):332-51. doi: 10.1902/jop.2012.120040. Epub 2012 May 21.
citation: Tamashiro NS, Duarte PM, Miranda TS, Maciel SS, Figueiredo LC, Faveri M, Feres M. Amoxicillin Plus Metronidazole Therapy for Patients with Periodontitis and Type 2 Diabetes: A 2-year Randomized Controlled Trial. J Dent Res. 2016 Jul;95(7):829-36. doi: 10.1177/0022034516639274. Epub 2016 Mar 24.