Melatonin Supports Non Surgical Periodontal Treatment in Patients With Type 2 Diabetes and Periodontitis
Condition: Diabetes Mellitus; Periodontitis; Melatonin; Matrix Metalloproteinases
MeSH terms: Periodontitis; Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      Background and aim: Hyperinflammatory host response associated with diabetes mellitus
      significantly provokes periodontal tissue destruction. In this context, supporting the
      standard treatment of periodontitis in diabetics with host modulation agents is a current
      field of study.

      This clinical study aims to investigate the clinical efficacy of melatonin supplementation in
      non-surgical periodontal treatment in patients with Type 2 DM and periodontitis and its
      biological basis (clinical effectiveness) based on some basic markers.

      Material and method: In this randomized controlled and double-blind study, 27 of 55 patients
      with diabetic periodontitis underwent full mouth scaling and root planning (fmSRP) alone and
      28 of them were administered melatonin (6 mg daily, for 30 days) in addition to fmSRP. The
      possible therapeutic contribution of melatonin was evaluated clinically and biochemically
      [gingival crevicular fluid (GCF) RANKL, OPG and MMP-8 and serum IL-1β levels] at 3 and 6
      months.
    

Detailed description: 
      Ethical Approval This double-blind and randomized controlled clinical study was carried out
      on 55 patients with Type 2 DM and periodontitis who applied to the Periodontology Clinic of
      the Faculty of Dentistry of Recep Tayyip Erdoğan University between 2021/February and
      2022/January and met the study criteria. Ethical approval was given by the Clinical Research
      Ethics Committee of the Faculty of Medicine of the same university within the framework of
      the Declaration of Helsinki (2008) (2022/03). The possible risks and benefits of the
      treatment to be applied to the participants were mentioned and their verbal and written
      consents were obtained.

      Working Groups According to the WHO, in individuals in the young age category, "stage 3/4
      periodontitis" was determined according to the current periodontal disease and condition
      classification as the diagnostic criterion for periodontitis. Accordingly, probing pocket
      depth (PPD) should be at least 6mm and bone loss should be at least 3mm. Our diagnostic
      criteria for Type 2 DM was fasting plasma glucose (FPG) level greater than 126 mg/dl and
      glycosylated hemoglobin level (HbA1c) greater than 6.5%. Those who smoke, use antibiotics,
      anti-inflammatory and antioxidant drugs in the last 6 months, work night shifts, are in
      pregnancy and lactation, have cancer and autoimmune diseases, have kidney disease, have
      received any periodontal treatment in the last 6 months obese patients were also excluded
      from the study. In Europe, obesity is defined as a body-mass index (BMI) of more than 30
      kg/m2 and a waist circumference of more than 88 cm in women and 102 cm in men.

      Treatment Protocol According to the above criteria, patients included in the study were
      randomly divided into control (fmSRP) and treatment [fmSRP-melatonin (fmSRP-mel)] groups by a
      computer program by an independent researcher (HA). The investigator (YSG), who provided the
      sample and conducted the clinical procedures, was blind to the study groups. fmSRP is the
      approach of completing supragingival and subgingival debridement procedures within 24 hours
      with periodontal curettes, scalers and ultrasonic instruments. Additional melatonin
      administration was made in the form of tablets containing 6mg of melatonin daily for 30 days
      from the day following the SRP. Patients were instructed to take the tablets just before
      bedtime. No additional application was made in the control group. Within the scope of the
      non-surgical periodontal treatment program, all patients were trained on brushing teeth with
      the modified bass technique and the use of appropriate interface cleaning tools. These
      trainings were repeated in the maintenance sessions. Participants were also instructed not to
      use any mouthwash.

      Sample Collection and Clinical Periodontal Measurements Clinical periodontal measurements
      with gingival crevicular fluid(GCF) and serum samples were performed at baseline (T0) and at
      3th (T1) and 6th months (T2) following fmSRP. In all three periods, sampling was done one day
      before clinical periodontal measurements.

      GCF samples were taken from the interproximal regions of the two teeth with the most
      radiographic bone loss in each of the four quadrants in the morning. Initially, proper
      isolation was achieved by means of cotton rolls. The area was slightly dried for 10 seconds.
      Sterile paper strips (Periopaper, Proflow, Inc., Amityviile, NY) were advanced until minimal
      resistance was felt in the sulcus. Waited 30 seconds. Paper strips contaminated with blood or
      saliva were not included. The GCF volume in each paper strip was measured using the periotron
      device (Periotron 8010 Harco Electronics, Winnipeg, Canada) by electrical compedance method
      and recorded as µl. Immediately afterwards, 8 paper strips obtained from each patient were
      transferred to an eppendorf tube containing 250 µl of phosphate buffer solution. It was
      stored in a -80°C freezer (Thermo Fisher Scientific, Waltham, MA, USA) until the day of
      biochemical analysis.

      Immediately following the GCF samples, 16 cc venous blood samples were taken from the left
      arm antecubital fossa region of the patients. After the blood was centrifuged at 3000 rpm at
      2-8oC for 15 minutes, serum samples were obtained (Elektro-mag, Istanbul, Turkey). The
      samples were taken into Eppendorf tubes and kept in a -80°C freezer (Thermo Fisher
      Scientific, Waltham, MA, USA) until the day of analysis.

      Plaque index (PI), gingival index (GI), bleeding on probing (BOP), PPD and clinical
      attachment level (CAL) measurements were performed for clinical periodontal status
      assessments. PPD was measured as the distance between the deepest point of the sulcus and the
      gingival margin, and CAL as the distance between the deepest point of the sulcus and the
      enamel-cementum junction. Scoring for each tooth was made from 6 different regions for PPD
      and CAL, and from 4 different regions for other indices. Williams periodontal probe
      (Hu-Friedy, Chicago, IL, USA) was used for measurements.

      Biochemical Analysis Eppendorf tubes, which were removed from the freezer 24 hours before the
      experiment, were allowed to thaw gradually, first at -20oC and then at +4oC. The samples and
      reagents were brought to room temperature (18-25oC) just before the analysis. RANKL (Catalog
      no: E-EL-H5813), OPG (Catalog no: E-EL-H1341) and MMP-8 (Catalog no: E-EL-H1450) analyzes in
      GCF samples, IL-1ß (Catalog no: E- EL-H0149) analyzes were performed on serum samples using
      the enzyme-linked immunosorbent assay (ELISA) method and according to the instructions of the
      kit manufacturer (Elabscience, Houston, Texas, USA). Results were calculated as ng/ml (MMP-8)
      and pg/ml (IL-1β, RANKL and OPG).

      Statistical Analysis Windows 17.0 for SPSS program was used for statistical analysis. (SPSS
      Inc., Chicago, USA) The conformity of the data to the normal distribution was evaluated with
      the Shapiro Wilk test. The Mann Whitney U test was used for intergroup comparisons, and the
      Friedman, Wilxocon tests and Bonferroni correction were used for the analysis of
      time-dependent within-group changes. Chi-square test was applied for comparison between
      groups in terms of genders. A p<0.05 level was considered statistically significant.
    

Intervention name(s): Melatonin 3 MG
Intervention type(s): Drug
Intervention description(s): In this clinical trial, all patients that have both diabetes mellitus and periodontitis were performed full mouth scaling and root planning in order to start their periodontal treatments. Different from the control group, in fmSRP-mel group's patients systemic melatonin tablets (6 mg daily, for 30 days) were given immediately after the fmSRP procedure in order to support the scaling and root planning.
Other intervention name(s): Melatonina 3mg
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment