Grape Seeds Extract Gel as an Adjunct for the Treatment of Chronic Periodontitis
Condition: Chronic Periodontitis
MeSH terms: Periodontitis; Chronic Periodontitis
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of this study was to formulate a mucoadhesive gel of grapes seed extract (GSE)
      followed by short-term clinical study for the effectiveness of this gel onto the pocket depth
      (PD), plaque index (PI), gingival index (GI), and bleeding on probing (BOP) when applied in
      periodontal pockets as an adjunct treatment for chronic periodontitis.
    

Detailed description: 
      Before commencing with the study, the trial proposal was registered in the research center
      and ethical clearance was taken from the ethical committee (FUGRP/2014/182)

      Materials used in the study::

        1. Pure Grape Seed Extract (GSE) supplied by pure bulk supplements (Bulksupplements, USA).
           It contains natural ingredient of more than 180 mg of proanthocyanidins for every 200 mg
           of serving size of the powder. GSE has been considered safe by the National Center for
           Complimentary and Integrative Health if used orally for up to 8 weeks of clinical trials

        2. Carbapol "CB 934" (Loba Chemie Pvt. Ltd., Mumbai)

        3. Sodium- carboxy methly cellulose "Na-CMC" supplied (Loba Chemie Pvt. Ltd., Mumbai)

        4. Sodium phosphate monobasic and sodium phosphate dibasic (Acros organic Ltd., Mumbai)

        5. Parabens (Loba Chemie Pvt. Ltd., Mumbai)

      Method of preparation:

      GSE mucoadhesive gel preparation:

      - Formula 1: 2% GSE mucoadhesive gel based on minimum inhibitory concentration (MIC) and
      minimum toxic concentration (MTC) and depending on the concentration of adhesive polymers
      that were added to the formula.

      Weighed CB 934 was dissolved in 50 ml of phosphate buffer of pH 6.6 with a vigorous mixing
      until it dissolved completely. Then, GSE and preservatives were dissolved in about 25 ml of
      phosphate buffer of pH 6.6. After that, the GSE solution was slowly added into the solution
      of CB 934 with a continuous stirring that was achieved by magnetic stirring at a speed of 100
      rpm until a homogenous mixture was obtained. The gelling agent (Na-CMC) was added slowly
      under a continuous magnetic stirring. Then, the volume was increased up to 100 ml with the
      addition of phosphate buffer. Finally, the prepared gel was kept for 24 hours at room
      temperature (25°C) for a complete polymer dissolution.

      - Formula 2: controlled gel without GSE. A controlled mucoadhesive gel was used in the
      clinical study to be compared with GSE gel. This control gel contained all above mentioned
      substances except for the GSE.

      Microbial limit test:

      One gram of the gel was suspended in 2.9 ml of phosphate buffer at pH 7.2. Different sterile
      media (Bismuth Sulfite Medium, Mannitol salt agar medium, Muller Hinton agar medium,
      cetrimide agar medium and sabaroud agar medium) were inoculated with the gel, then, incubated
      for 24 hours. After that, the media were examined to ensure no growth of bacterial genera.

      Subjects:

      A random sample of 24 patients were screened and examined. Five patients with mean age 43.5
      ±7.9 years were found to comply with the study inclusion criteria

      Baseline measurements and application of gels A total of 86 Sites of pocket depth (PD) of 5
      mm and above were identified. Sites were divided randomly by split mouth technique into two
      groups: Test group (GSE group) who will receive GSE mucoadhesive gel (N=48) and Control group
      who will receive the control gel (N=38). The two prepared formulas were placed in identical
      containers providing that neither the patient, nor the clinician were aware of which was
      applied on which quadrant of the mouth "i.e. double blinded study".

      In the first visit, an informed written consent was obtained from all patients. scaling and
      root planing (SRP) were performed by the same calibrated examiner using an ultrasonic scaler
      (miniPiezon, EMS, Switzerland) and Gracey curettes (Hu-Friedy Mfg, USA). Seven days after,
      the patients were recalled for clinical examination and baseline measurement (T0) were taken
      for Plaque index (PI), Gingival index (GI), Pocket depth (PD), and bleeding on probing (BOP)
      by a single calibrated examiner. PD was measured using a manual probe (UNC 15). PI and GI
      were assessed according to Silness and Loe (1964). BOP was assessed within 30 seconds after
      probing. In the same visit, the examiner applied the two prepared formulas into two opposite
      quadrants using a disposable syringe with a 23-gauge needle. Patients were given oral hygiene
      instructions and were instructed not to drink or eat for a minimum of 3 hours, not to brush
      the area for 24 hours and not to use mouth wash during the course of treatment.

      The patients were recalled again after 3, 6, and 9 days to reapply the two formulas in the
      examined sites by the same examiner.

      Revaluation The first re-evaluation visit (T1) was after 28 days from the baseline
      measurements (T0). During this visit, the calibrated clinician measured and recorded PI, GI,
      PD, BOP for all examined sites.

      The second re-evaluation visit (T2) was after 6 months from the baseline measurements (T0)
      and the same measurements were retaken for all sites.

      Statistical Package for the Social Sciences (SPSS) v20 package (IBM Corp) was used for
      statistical analysis. Significance of the change in PI, GI, and PD within each group were
      determined using paired t-test while the significance of difference in the change between the
      two groups was determined using the independent t-test. The difference was considered
      statistically significant at p < 0.05.
    

Intervention name(s): 2% GSE mucoadhesive gel; GSE free mucoadhesive gel
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 2% GSE mucoadhesive gel administered in periodontal pockets of GSE group at T0 and 3, 6, and 9 days after T0; GSE free mucoadhesive gel administered in periodontal pockets of Control group at T0 and 3, 6, and 9 days after T0
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment